The DOI matches its Crossref record; 70 of the 74 references it cites were found in a registry or an index; 14 of the 43 sources its claims cite were checked for support.
Modulation of K-Ras-Dependent Lung Tumorigenesis by MicroRNA-21
Open accessAbstract
Lung cancer is the leading cause of cancer-related deaths in the world, and non-small-cell lung cancer (NSCLC) accounts for 80% of cases. MicroRNA-21 (miR-21) expression is increased and predicts poor survival in NSCLC. Although miR-21 function has been studied in vitro with cancer cell lines, the role of miR-21 in tumor development in vivo is unknown. We utilize transgenic mice with loss-of-function and gain-of-function miR-21 alleles combined with a model of NSCLC to determine the role of miR-21 in lung cancer. We show that overexpression of miR-21 enhances tumorigenesis and that genetic deletion of miR-21 partially protects against tumor formation. MiR-21 drives tumorigenesis through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis.
Overview
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Written from the paper’s full text.
TL;DR
In a K-rasLA2 mouse model of NSCLC, miR-21 overexpression increased lung tumor number/area and proliferation, while miR-21 deletion reduced tumor burden and sensitized transformed MEFs to doxorubicin-induced apoptosis. miR-21 acts as a tumor promoter by repressing Ras/MEK/ERK negative regulators (Spry1, Spry2, Btg2, Pdcd4) and pro-apoptotic genes (Apaf1, Faslg, Pdcd4, RhoB).
Key findings
- CAG-miR-21;K-rasLA2 mice overexpressing miR-21 4–6 fold had significantly more gross lung tumors at 18 weeks and increased microscopic tumor number and total tumor area versus K-rasLA2 littermates; tumors showed increased proliferation, but survival did not differ, possibly due to decreased thymic tumor incidence.
- miR-21−/−;K-rasLA2 mice had significantly fewer surface lung tumors at 20 weeks and decreased total tumor area; no adenocarcinomas were noted in any of 14 miR-21−/−/K-rasLA2 animals evaluated, and miR-21 deletion did not alter Ki67 proliferation.
- miR-21 overexpression alone was not sufficient for tumorigenesis: CAG-miR-21 mice without K-rasLA2 (n = 39) followed up to 555 days showed no tumors.
- Reporter assays showed 13 of 24 putative mouse miR-21 target 3′UTRs were repressed by miR-21, with mutation of the miR-21 site abrogating repression in 11; in tumors, miR-21 overexpression decreased Spry1, Spry2, Btg2, Pdcd4, Apaf1, Faslg, and RhoB and increased ERK phosphorylation. K-ras activation increased miR-21 expression 4-fold; miR-21−/− MEFs formed fewer soft agar colonies and smaller xenograft tumors and showed increased doxorubicin-induced apoptosis.
Methods
- Generated conditional CAG-miR-21 overexpressing and miR-21−/− mice, crossed to the K-rasLA2 NSCLC model; comparisons were to littermate controls, with tumor burden assessed by H&E/ImageJ, proliferation by Ki67, and apoptosis by TUNEL.
- MEFs from wild-type and miR-21−/− mice were immortalized with SV40 large T/small t and transformed with H-rasG12V; assays included soft agar, xenografts, doxorubicin treatment (100 nM–10 μM for 12 h), and TUNEL (1 μM for 12 h).
- Luciferase reporter assays tested 24 putative miR-21 target 3′UTRs; Western blots were performed on micro-dissected tumors; statistics used two-tailed unpaired Student’s t-test with p < 0.05 considered significant.
Limitations
- No formal limitations section is present; the authors state miR-21 overexpression alone was not sufficient for tumorigenesis and that tumors arising after miR-21 deletion may have developed escape mechanisms, possibly explaining latency.
- The text notes miR-21 deletion did not alter apoptosis in lung lesions, suggesting those tumors escaped miR-21 regulatory effects; no adenocarcinomas were observed in 14 miR-21−/−;K-rasLA2 animals, a limited sample for that endpoint.
- Evident from the text: all mice used were of mixed genetic backgrounds, and findings are from a mouse K-rasLA2 model and transformed MEFs, so human NSCLC causality and therapeutic implications remain to be tested.
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Claims the paper makes
14 of 43 cited sources checked · 6 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Four of the validated miR-21 target genes are known negative regulators of the Ras/MEK/ERK pathway: sprouty 1 (Spry1), sprouty 2 (Spry2), B-cell translocation gene 2 (Btg2), and programmed cell death 4 (Pdcd4).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
What the sources say
- Partly supportedcites Casci et al., 1999 sourceExperimental — accuracy not yet measured
The Discussion identifies Drosophila Sprouty as an inhibitor of Ras/MAP kinase signaling. The paper predicts that mammalian Sprouty homologs may have the same function, but does not establish it for Spry1 or Spry2 specifically. It does not address Btg2, Pdcd4, or whether these genes are validated miR-21 targets. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites Hanafusa et al., 2002 source
- Not matchedcites Lo et al., 2006
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
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In the paper
“Oncogenic Ras activation has been shown to increase the expression of Spry2, providing feedback inhibition of Ras activation (Shaw et al., 2007).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Partly supportedcites Shaw et al., 2007 sourceExperimental — accuracy not yet measured
In “Negative feedback signaling in development” (page not available), the paper reports that oncogenic K-ras up-regulates Spry-2 and that Spry-2 inhibits MAPK activation. It does not establish that Spry-2 inhibits activation of Ras itself; it describes possible effects at different points in the Ras/MAPK pathway, including downstream of activated K-ras. (LLM, conf=0.86)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show that over-expression of miR-21 enhances tumorigenesis and genetic deletion of miR-21 partially protects against tumor formation.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > Abstract
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In the paper
“We show that over-expression of miR-21 enhances tumorigenesis and genetic deletion of miR-21 partially protects against tumor formation.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“K-ras activation in the tumors of K-rasLA2 mice increased miR-21 expression 4-fold similar to the expression level in the CAG-miR-21 transgenic mouse lung.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > Oncogenic Ras activation increases miR-21 expression In vivo
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In the paper
“Total tumor area as a proportion of total lung area was significantly decreased with miR-21 deletion (Figure 2D).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 over-expression in CAG-miR-21;K-rasLA2 mutant tumors decreases Spry1, Spry2, and Btg2 protein expression compared to K-rasLA2 tumors (Figure 4C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This is may be explained by a decreased incidence of thymic tumors in CAG-miR-21;K-rasLA2 mutant mice compared to K-rasLA2 controls (Figure 1I), thus contributing to the enhanced survival.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“There was no difference in proliferation between the miR-21−/− and wild type MEFs (Figure S2C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses Ras-driven transformation In vitro
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In the paper
“Total tumor area as a proportion of total lung area was significantly increased with miR-21 over-expression (Figure 1E).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite the increased tumor burden, the survival of CAG-miR-21;K-rasLA2 mutant mice did not differ from K-rasLA2 control mice (Figure 1H).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
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In the paper
“and microscopically on H&E cross-section over all time points (Figure 1F).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Global miR-21 over-expression was achieved by breeding the CAG-Z-miR21-EGFP mouse to transgenic mice expressing Cre recombinase from the ubiquitous CAG promoter resulting in the CAG-miR-21 mouse, which globally over-expressed miR-21 4–6 fold over normal levels of expression (Figure S1B–D).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Multiple negative regulators of the Ras/MEK/ERK pathway were shown to be direct miR-21 target genes by luciferase reporter assays (Figure 3B).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The luciferase reporter assays in COS cells reflect endogenous miR-21 target regulation in mouse lung tumors.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the miR-21−/− MEFs formed significantly less colonies in soft agar than wild type MEFs (Figure S2D)”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses Ras-driven transformation In vitro
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Compared to K-rasLA2 littermates, CAG-miR-21;K-rasLA2 mice displayed significantly more lung tumors visible grossly at 18 weeks (Figure 1D)”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lysates from individually isolated tumors from CAG-miR-21;K-rasLA2 mice showed decreased expression of Apaf1, Caspase 3, Pdcd4, Faslg and RhoB (Figures 4C and 5D).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 suppresses apoptosis by targeting proapoptotic genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Approximately 180 mRNAs are predicted as miR-21 target genes based on the presence of miR-21 sites in their 3′ UTRs.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although not statistically significant, there was a trend towards decreased conversion of hyperplasia to adenoma in the miR-21−/−;K-rasLA2 mice (Figure 2H).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and developed smaller tumors in xenografts in nude mice (Figure S2E).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses Ras-driven transformation In vitro
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No adenocarcinomas were noted in any of the 14 miR-21−/−/K-rasLA2 animals evaluated.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21−/−;K-rasLA2 mutant mice displayed a reduced incidence of hyperplasic lesions and adenomas compared to K-rasLA2 controls (Figure 2G).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Deletion of miR-21 had no effect on the amount of apoptosis in the lung lesions as detected by TUNEL suggesting that lung tumors that develop in the background of the genetic deletion of miR-21 have escaped miR-21 regulatory effects (Figure 5C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 suppresses apoptosis by targeting proapoptotic genes
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Remarkably, over-expression of miR-21 enhanced the number of tumors in this model of lung cancer (Figure 1A–C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Reporter assays in COS cells revealed miR-21 dependent repression of 13 of the 24 3′UTRs”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The luciferase reporter assays in COS cells reflect endogenous miR-21 target regulation in mouse lung tumors.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In CAG-miR-21;K-rasLA2 tumors, miR-21 expression was more than additive compared to either CAG-miR-21 or K-rasLA2 mice alone.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > Oncogenic Ras activation increases miR-21 expression In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 over-expression in CAG-miR-21;K-rasLA2 mice reduced apoptosis in lung tumors as shown by TUNEL staining (Figure 5A and 5B).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 suppresses apoptosis by targeting proapoptotic genes
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In the paper
“MiR-21 over-expression did not increase the rate of recombination of the K-rasLA2 allele (Figure S1F).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Normal lung tissue from K-rasLA2 mice (prior to K-ras activation) exhibits wild type expression levels of miR-21 (Figure 4A and 4B).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > Oncogenic Ras activation increases miR-21 expression In vivo
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In the paper
“MiR-21−/−;K-rasLA2 mutant tumors did not show alteration in the regulation of ERK by Spry1, Spry2, and Btg2 (Figure 4D).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We followed CAG-miR-21 mice (n = 39) without K-rasLA2 for up to 555 days and performed full necropsy and histological analysis on H&E sections the following tissues: lung, heart, brain, spleen, liver, kidney, stomach, colon, skeletal muscle, and bone marrow. No tumors were observed in CAG-miR-21 mice without K-rasLA2”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Protein analysis of individually isolated tumors showed that Pdcd4 levels were decreased in CAG-miR-21;K-rasLA2 compound mutant mice compared to K-rasLA2 control tumors (Figure 4C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Eleven of the putative miR-21 target gene 3′ UTRs including phosphatase and tensin homolog (Pten) were not repressed by miR-21 (Figure 3B).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Tumors in CAG-miR-21;K-rasLA2 mice exhibited increased proliferation compared with K-rasLA2 control tumors (Figure 1G).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21−/−;K-rasLA2 mutant tumors did not show alteration in the regulation of Apaf1 or Faslg (Figure 5E).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 suppresses apoptosis by targeting proapoptotic genes
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 deletion did not alter proliferation in tumors measured by Ki67 staining (Figure 2E).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Several pro-apoptotic genes were directly targeted by miR-21, apoptotic peptidase activating factor 1 (Apaf1), Fas ligand (Faslg), Pdcd4, and ras homolog gene family member B (RhoB).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This regulation was absent in tumors from the miR-21−/−;K-rasLA2 compound mutant mice (Figure 4D).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Significantly less tumors were present on the surface of the lungs of 20 week-old miR-21−/−;K-rasLA2 compound mutant mice compared to K-rasLA2 control mice (Figure 2A–C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and mutation of the miR-21 site in the 3′ UTR abrogated the repression in 11 of the putative target gene 3′ UTRs (Figure 3A).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The luciferase reporter assays in COS cells reflect endogenous miR-21 target regulation in mouse lung tumors.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“as well as decreased expression of Faslg a key initiator of the extrinsic, death receptor apoptotic pathway.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“modulates NSCLC tumorigenesis by targeting Spry1, Spry2, Btg2, and Pdcd4”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > EXPERIMENTAL PROCEDURES > Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Spry1, Spry2, Btg2, and Pdcd4 act as negative regulators of the Ras/MEK/ERK pathway.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show in vivo that miR-21 expression increases with oncogenic K-ras activation”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > EXPERIMENTAL PROCEDURES > Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The increased sensitivity to doxorubicin-induced measure by cleaved caspase 3 levels was confirmed by TUNEL (Figure 6C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion sensitizes cells to DNA-damaging chemotherapy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Over-expression of miR-21 correlated with a decrease RhoB protein levels.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and Apaf1, Faslg, Pdcd4 and RhoB which promote apoptosis.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > EXPERIMENTAL PROCEDURES > Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Apaf1, Faslg, Pdcd4 and RhoB promote apoptosis.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The present work illustrates in vivo that increased expression of miR-21 significantly reduces apoptosis in mouse lung tumors.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased sensitivity to DNA-damaging agents in the miR-21−/− transformed MEFs suggests that inhibition miR-21 could provide a therapeutic strategy in NSCLC.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 deletion also sensitizes cells to DNA-damaging chemotherapy, suggesting that miR-21 inhibition could be of therapeutic value.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > EXPERIMENTAL PROCEDURES > Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Lentiviral over-expression of miR-21 decreased cleaved caspase 3 levels compared to empty lentiviral transduced miR-21−/− MEFs.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion sensitizes cells to DNA-damaging chemotherapy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MEFs from miR-21−/− mice display increased sensitivity to doxorubicin-induced apoptosis measured by protein levels of cleaved caspase 3 (Figure 6A).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion sensitizes cells to DNA-damaging chemotherapy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 over-expression resulted in reduced protein levels of Apaf1 a key component of the intrinsic, mitochondrial apoptotic pathway”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results suggest that in vitro miR-21 can repress multiple tumor suppressor genes that may participate in tumorigenesis.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These observations suggest that miR-21 actively participates in Ras-driven transformation.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses Ras-driven transformation In vitro
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These results illustrate that miR-21 deletion suppresses tumor development In vivo.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“No tumors were observed in CAG-miR-21 mice without K-rasLA2, indicating that miR-21 over-expression alone is not sufficient for tumorigenesis.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“Faslg mRNA is expressed normally in human lung tumors; however, the Faslg protein is only detected in a small fraction (Badillo-Almaraz et al., 2003).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Badillo-Almaraz et al., 2003 source
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIn the paper
“Faslg mRNA is expressed normally in human lung tumors; however, the Faslg protein is only detected in a small fraction (Badillo-Almaraz et al., 2003).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Badillo-Almaraz et al., 2003 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-21 was not sufficient in our model for tumorigenesis; however, under the control of other tissue-specific promoters, miR-21 could have cancer related phenotypes.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, inhibiting miR-21 potentially restores the activity of multiple tumor suppressors acting at various critical nodes of tumor development.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Spry1, Spry2, Btg2, and Pdcd4 act as negative regulators of the Ras/MEK/ERK pathway.
- Rests on an assumption: Apaf1, Faslg, Pdcd4 and RhoB promote apoptosis.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 deletion also sensitizes cells to DNA-damaging chemotherapy, suggesting that miR-21 inhibition could be of therapeutic value.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > EXPERIMENTAL PROCEDURES > Statistical Analysis
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIn the paper
“RhoB expression is down-regulated in human NSCLC suggesting a role as a tumor suppressor gene (Sato et al., 2007).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Sato et al., 2007 source
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Increased sensitivity to DNA-damaging agents in the miR-21−/− transformed MEFs suggests that inhibition miR-21 could provide a therapeutic strategy in NSCLC.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results define in vivo an autoregulatory loop between oncogenic Ras and miR-21 mediated by Spry1, Spry2, Btg2, and Pdcd4.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-21 mediated translational inhibition could partially explain this finding.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“By targeting antagonists of Ras/MEK/ERK signaling and pro-apoptotic genes, miR-21 enhances tumor proliferation and survival, two critical components of tumor promotion.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The genetic deletion of miR-21 removes the miR-21 mediated down-regulation of Spry2 resulting in more Spry2-mediated Ras/MEK/ERK inhibition and tumor suppressor activity.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Here we report an in vivo, functional role of miR-21 in non-small cell lung cancer.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: Spry1, Spry2, Btg2, and Pdcd4 act as negative regulators of the Ras/MEK/ERK pathway.
- Rests on an assumption: Apaf1, Faslg, Pdcd4 and RhoB promote apoptosis.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, miR-21 plays a significant role in inhibition of apoptosis thus allowing tumor survival.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion sensitizes cells to DNA-damaging chemotherapy
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- Probably not a substantial claim. 25
- It may state two separate claims as one. 35
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Recently, miR-21 expression levels have proven useful prognostic markers in non-small cell lung cancer (Markou et al., 2008; Yanaihara et al., 2006).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
- Supportedcites Markou et al., 2008 source
The discussion reports that mature miR-21 overexpression in NSCLC was associated with lung-cancer death and was an independent prognostic factor in multivariate analysis. The authors caution that the small number of events requires further confirmation, so the finding should not be read as a validated clinical test. (LLM, conf=0.88)
- Partly supportedcites Yanaihara et al., 2006 sourceExperimental — accuracy not yet measured
The Results report that high hsa-mir-21 expression was associated with significantly worse survival in lung adenocarcinoma patients. They do not establish miR-21 as a validated prognostic marker across non-small cell lung cancer: the reported prognostic validation focused on other miRNAs. (LLM, conf=0.88)
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“The level of miR-21 expression in sputum distinguishes NSCLC patients from cancer-free controls with a greater sensitivity than conventional cytology (Xie et al., 2009).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
- Supportedcites Xie et al., 2009 source
The Results section, under “Comparison of cytology and measurement of altered miRNA expression in sputum,” reports 69.66% sensitivity for sputum miR-21 measurement versus 47.82% for conventional sputum cytology. The study examined sputum from 23 NSCLC patients and 17 cancer-free subjects, matching the claimed comparison. (LLM, conf=0.95)
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Several components of the PI3K pathway, including PTEN and PIK3R1, have been suggested as miR-21 target genes (Meng et al., 2007); however, miR-21 over-expression did not alter PTEN and PIK3R1 protein expression or Akt phosphorylation (Figure S3B).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
What the sources say
- Partly supportedcites Meng et al., 2007 sourceExperimental — accuracy not yet measured
The Results identify PTEN as a miR-21 target, and the Discussion places PTEN in the PI3K pathway. The passages do not identify PIK3R1 as a miR-21 target. The statement that over-expression did not alter protein expression or Akt phosphorylation is attributed to the citing paper’s Figure S3B, not to Meng et al. (LLM, conf=0.87)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Targeted deletion of miR-21 in RKO and DLD1 colon cancer cells revealed miR-21 contributes to tumorigenesis through compromising cell cycle progression and DNA damage-induced checkpoint function through the Cdc25a target gene (Wang et al., 2009).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
- Partly supportedcites Wang et al., 2009 sourceExperimental — accuracy not yet measured
The Results report targeted miR-21 deletion in RKO and DLD1 cells, and the Discussion links miR-21, Cdc25A, cell-cycle progression, and checkpoint activation. However, the Discussion describes a contribution to tumorigenesis as a possibility, not a demonstrated outcome; the claim's “revealed” overstates that conclusion. (LLM, conf=0.88)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“As well, epidermal growth factor receptor (EGFR) and HER2/neu signaling positively regulates miR-21 expression in human lung and breast carcinoma cell lines, respectively (Huang et al., 2009; Seike et al., 2009).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > Oncogenic Ras activation increases miR-21 expression In vivo
What the sources say
- Supportedcites Huang et al., 2009 source
The paired citations and “respectively” attribute the HER2/neu finding in breast carcinoma cells to Huang et al. In “Ectopic Expression of HER2/neu Induces miR-21 Upregulation” (Fig. 1A; page not provided), the paper reports that HER2/neu expression increased miR-21 in a human breast cancer cell line. The EGFR finding in lung cells is not attributed to this source. (LLM, conf=0.94)
- Not checked — no full text of the sourcecites Seike et al., 2009 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Zhang et al. showed in a human gastric cancer cell line that forced over-expression of miR-21 enhanced tumor proliferation and invasion”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Supportedcites Zhang et al., 2008 source
In the Results sections on proliferation and invasion (page numbers not provided), the paper reports that transfecting AGS human gastric cancer cells with a miR-21 expression construct significantly increased proliferation and strengthened invasion. This matches the claim about forced over-expression in a human gastric cancer cell line. (LLM, conf=0.94)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“SPRY2, in turn, negatively regulates Ras/MEK/ERK signaling and is a tumor suppressor in NSCLC in both mice (Minowada and Miller, 2004; Minowada and Miller, 2009; Shaw et al., 2007) and humans (Sutterluty et al., 2007).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Minowada and Miller, 2004 source
- Partly supportedcites Minowada and Miller, 2009 sourceExperimental — accuracy not yet measured
The study summary and Discussion (page unavailable) report fewer and smaller urethane-induced lung tumors in mice overexpressing Sprouty 2, supporting a tumor-suppressive effect in that mouse model. The Discussion says the findings are consistent with antagonism of Ras signaling, but the mechanism remains unclear; this paper does not demonstrate inhibition of MEK/ERK signaling. The citing sentence attributes the human NSCLC portion to a separate citation, not to this paper. (LLM, conf=0.83)
- Supportedcites Shaw et al., 2007 source
The Negative feedback signaling in development section reports that Spry-2 inhibits MAPK activation in K-ras G12D mouse lungs. The tumor-suppression section concludes that Spry-2 limits K-ras-driven mouse lung tumor development; a correction in Additional information says its revised results do not change that conclusion. The citing sentence attributes the human finding to Sutterluty et al., not to this paper. (LLM, conf=0.90)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“All tumors from the survival cohort were analyzed on H&E sections and categorized as hyperplasia, atypical adenomatous hyperplasia, adenoma, adenoma with typia, and adenocarcinoma according to the Mouse Models of Human Cancer Consortium recommendations.(Nikitin et al., 2004)”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > EXPERIMENTAL PROCEDURES > Tumor Grading
What the sources say
- Partly supportedcites Nikitin et al., 2004 sourceExperimental — accuracy not yet measured
The Development of Recommendations section says the consortium prepared and reviewed H&E-stained sections, and the classification defines hyperplasia, atypical adenomatous hyperplasia, adenoma, and adenocarcinoma. The cited paper does not identify “adenoma with typia” as a recommended category. The survival-cohort analysis describes the citing authors’ own work, not an analysis reported by Nikitin et al. (LLM, conf=0.85)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“knock-down of miR-21 resulted in a marked reduction in proliferation and increase in apoptosis (Zhang et al., 2008).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Supportedcites Zhang et al., 2008 source
The Abstract states that inhibiting miR-21 in AGS human gastric cancer cells significantly reduced proliferation and increased apoptosis. The ‘miR-21 Increases Cell Proliferation and Inhibits Cell Apoptosis’ section reports both effects after transfection with an anti-miR-21 inhibitor. (LLM, conf=0.95)
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Methods have been developed to manipulate miRNA function pharmacologically, facilitating the development of new cancer therapeutic strategies (Hutvagner et al., 2004; Krutzfeldt et al., 2005).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Partly supportedcites Hutvagner et al., 2004 sourceExperimental — accuracy not yet measured
The Results and Discussion report that 2′-O-methyl oligonucleotides inhibit specific miRNAs and can be used to study their function in C. elegans. The paper presents them as a research tool; it does not establish that they facilitate new cancer therapeutic strategies. (LLM, conf=0.87)
- Not checked — no full text of the sourcecites Krutzfeldt et al., 2005 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“RECK, Cdc25a, Map2k3, NfiB, Trp63 and Ski have been shown to be miR-21 target genes in vitro, but only RECK showed decreased protein levels in the CAG-miR-21;K-rasLA2 tumors (Figure S3A).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR21−/−;K-rasLA2 mice all develop lung tumors, but show an increased incidence of thymic lymphoma (Figure 2F).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Caspase 3 and K-ras do not contain miR-21 sites in their 3′ UTR and the 3′ UTR luciferase reporter activity is not suppressed by miR-21 (Figure 3B).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The decrease in Spry1, Spry2, and Btg2 in CAG-miR-21;K-rasLA2 tumors correlates with increased Ras pathway activity, shown by increased ERK phosphorylation (Figure 4C).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show miR-21 dependent repression of the mouse Apaf1 3′ UTR reporter; however, the miR-21 site in the human APAF1 3′ UTR is conserved in primates but not conserved in the mouse.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple tumor suppressor genes
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“adult male CAG-miR-21 mice showed no signs of heart failure compared to littermate controls (Figure S1E)(van Rooij et al., 2006; van Rooij et al., 2008).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Apaf1, Pdcd4, Faslg, and RhoB were validated as direct miR-21 target genes by luciferase reporter assays; however, caspase 3 was not directly regulated by miR-21 (Figure 3B).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 suppresses apoptosis by targeting proapoptotic genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The luciferase reporter assays in COS cells reflect endogenous miR-21 target regulation in mouse lung tumors.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 over-expression increased the incidence of all tumor grades without increasing the rate of conversion to adenocarcinoma, suggesting that miR-21 participates in tumor promotion rather than progression and metastasis in this model (Figure 1J and 1K).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Unlike K-rasLA1;p53−/− compound mutant mice (Johnson et al., 2001), we did not observe an increased tumor spectrum or increased metastasis in the CAG-miR-21;K-rasLA2 mutant mice.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Although miR-21 function has been studied in vitro using cancer cell lines, the role of miR-21 in tumor development in vivo is unknown.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“MiR-21 drives tumorigenesis through inhibition of negative regulators of the Ras/MEK/ERK pathway and inhibition of apoptosis.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“A large scale survey to determine the miRNA signature of 540 tumor samples including lung, breast, stomach, prostate, colon, and pancreatic tumors and their respective normal adjacent tissue revealed miR-21 was the only miRNA up-regulated in all these tumors (Volinia et al., 2006).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Volinia et al., 2006 source
Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Further miRNA profiling in tumor samples and cancer cell lines show increased miR-21 expression in glioblastoma (Chan et al., 2005; Ciafre et al., 2005), head and neck carcinomas (Tran et al., 2007), ovarian cancer (Iorio et al., 2007), B-cell lymphoma (Lawrie et al., 2007), hepatocellular (Meng et al., 2007), and cervical carcinoma (Lui et al., 2007).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“CAG-miR-21 transgenic mice were viable, fertile and born in expected Mendelian ratios.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
In the paper
“Knock-down of miR-21 in the metastatic breast cancer MD-MBA-231 cells reduced invasion and metastasis (Zhu et al., 2008).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Zhu et al., 2008 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Homozygous miR-21 knock-out mice are viable, fertile, and born in expected Mendelian ratios without any gross phenotypic differences compared to wild type or heterozygous littermates, and without a cardiac phenotype (D.P., E.V.R. and E.N.O., manuscript in preparation).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 deletion suppresses Ras-driven transformation In vitro
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Rests on an assumption: The miR-21 knockout mice do not have compensatory molecular changes that confound the interpretation of tumorigenesis experiments.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data illustrate that miR-21 over-expression decreases the protein expression of four miR-21 target genes that are involved in apoptosis thus promoting survival.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 suppresses apoptosis by targeting proapoptotic genes
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
- Rests on an assumption: The luciferase reporter assays in COS cells reflect endogenous miR-21 target regulation in mouse lung tumors.
In the paper
“miR-21 expression was induced by AP-1 in response to Ras activation, and miR-21 mediated Ras-dependent downregulation of Pdcd4 (Talotta et al., 2009)”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > Oncogenic Ras activation increases miR-21 expression In vivo
What the sources say
- Not checked — no full text of the sourcecites Talotta et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
In the paper
“Knockdown of miR-21 in cultured glioblastoma cells activates caspases leading to apoptotic cell death, suggesting miR-21 is an anti-apoptotic factor (Chan et al., 2005).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
- Not checked — no full text of the sourcecites Chan et al., 2005 source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“K-rasLA2 mice develop multi-focal lung tumors with 100% penetrance, and less frequently develop thymic lymphomas and skin papillomas (Johnson et al., 2001).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
What the sources say
- Not checked — no full text of the sourcecites Johnson et al., 2001 source
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data suggest that miR-21 over-expression in human tumors does not simply reflect cancer pathology, but instead enhances aspects of the pathology of NSCLC.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 over-expression promotes tumor development In vivo
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
- Rests on an assumption: The level of miR-21 over-expression achieved in CAG-miR-21 mice (4–6 fold) is representative of the increased miR-21 expression in human NSCLC.
In the paper
“Previously, an autoregulatory loop connecting miR-21 and Ras activation through AP-1 was illustrated in a rat thyroid cell system (Talotta et al., 2009).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > Oncogenic Ras activation increases miR-21 expression In vivo
What the sources say
- Not checked — no full text of the sourcecites Talotta et al., 2009 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These data show that miR-21 over-expression decreases the protein expression of four miR-21 target genes that are tumor suppressors and negative regulators of the Ras/MEK/ERK pathway resulting in a concomitant increased ERK activity.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > RESULTS > miR-21 targets multiple negative regulators of Ras signaling
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
- Rests on an assumption: The luciferase reporter assays in COS cells reflect endogenous miR-21 target regulation in mouse lung tumors.
In the paper
“In breast cancer MCF-7 cells, miR-21 knock-down results in suppression of cell growth in vitro and tumor growth in xenografts (Si et al., 2007).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > INTRODUCTION
What the sources say
- Not matchedcites Si et al., 2007
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Not matched
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All mice used in these studies were of mixed genetic backgrounds and all comparisons were performed on littermate controls.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > EXPERIMENTAL PROCEDURES > Mouse Strains
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“PDCD4 is a pro-apoptotic tumor suppressor gene and has been verified as a miR-21 target in human colorectal and breast cancer cell lines (Afonja et al., 2004; Asangani et al., 2007; Bitomsky et al., 2008; Frankel et al., 2007; Lu et al., 2008; Zhang et al., 2006).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“In laryngeal carcinoma, miR-21 targets BTG2 (Liu et al., 2009), a p53 target gene, recently shown to suppress oncogenic Ras activity by reducing the GTP bound, active state (Buganim et al., 2010).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Knock-down of miR-21 in glioblastoma cell lines triggers the activation of caspases and increases apoptosis (Chan et al., 2005).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Chan et al., 2005 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“RhoB promotes growth inhibition and induces apoptosis in cancer cells (Kim et al., 2009)”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Kim et al., 2009 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the reductions in protein levels of individual miR-21 targets appear modest with miR-21 over-expression, collectively this diminution of tumor suppressor activity allows for more robust tumor formation through relieving multiple nodes of inhibition of the Ras/MEK/ERK pathway, thus facilitating tumor proliferation.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
- Rests on an assumption: The antibodies used in Western blots specifically detect the intended target proteins.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show that Ras activation increases miR-21 expression and in turn decreasing the expression of Spry2.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“miR-21 modulates several components critical to NSCLC pathogenesis through both relieving antagonism of the Ras pathway and reducing apoptotic effectors (Figure 7).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
In the paper
“RhoB expression is down-regulated in human NSCLC suggesting a role as a tumor suppressor gene (Sato et al., 2007).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Sato et al., 2007 source
Strength:hedged· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Relieving miR-21 inhibition of pro-apoptotic genes could provide a means to augment the effect of current chemotherapy.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Rests on an assumption: Apaf1, Faslg, Pdcd4 and RhoB promote apoptosis.
In the paper
“MiR-21 targets SPRY2 in cardiomyocytes and SW480 colon cancer cells, enhancing cell migration (Sayed et al., 2008).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Sayed et al., 2008 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our results show that miR-21 expression modulates tumor number, incidence and size in a mouse lung cancer model initiated by oncogenic K-rasG12D, consistent with miR-21 functioning as a tumor promoter.”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
- Rests on an assumption: The level of miR-21 over-expression achieved in CAG-miR-21 mice (4–6 fold) is representative of the increased miR-21 expression in human NSCLC.
In the paper
“Pdcd4 functions both as an inducer of apoptosis and a suppressor of AP-1 activity (Hwang et al., 2007).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Hwang et al., 2007 source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Loss of PDCD4 expression in human lung cancer correlates with higher grade and disease stage (Chen et al., 2003).”
§ Modulation of K-ras-dependent lung tumorigenesis by microRNA-21 > DISCUSSION
What the sources say
- Not checked — no full text of the sourcecites Chen et al., 2003 source
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
The K-rasLA2 mouse model is a valid model of human NSCLC for studying miR-21.
“To explore the role of miR-21 in the pathogenesis of NSCLC, we utilized the K-rasLA2 murine lung cancer model, which harbors a targeted, latent K-ras G12D allele that is activated by two distinct recombination events (Johnson et al., 2001).”
The paper relies on this without support.
The level of miR-21 over-expression achieved in CAG-miR-21 mice (4–6 fold) is representative of the increased miR-21 expression in human NSCLC.
“which globally over-expressed miR-21 4–6 fold over normal levels of expression (Figure S1B–D).”
The paper relies on this without support.
The miR-21 knockout mice do not have compensatory molecular changes that confound the interpretation of tumorigenesis experiments.
“Homozygous miR-21 knock-out mice are viable, fertile, and born in expected Mendelian ratios without any gross phenotypic differences compared to wild type or heterozygous littermates, and without a cardiac phenotype (D.P., E.V.R. and E.N.O., manuscript in preparation).”
The paper relies on this without support.
The antibodies used in Western blots specifically detect the intended target proteins.
“We isolated individual tumors from mice, made whole tumor lysates, and performed Western blots for putative miR-21 targets to address the effect of miR-21 expression on the protein levels of the miR-21 target genes in vivo within lung tumors.”
The paper relies on this without support.
The luciferase reporter assays in COS cells reflect endogenous miR-21 target regulation in mouse lung tumors.
“Reporter assays in COS cells revealed miR-21 dependent repression of 13 of the 24 3′UTRs”
The paper relies on this without support.
MicroRNAs are small non-coding RNAs that are commonly dysregulated in human malignancies and play a substantial role in the pathogenesis and survival of many cancers.
“MicroRNAs are small non-coding RNAs that are commonly dysregulated in human malignancies and play a substantial role in the pathogenesis and survival of many cancers.”
The paper relies on this without support.
MiR-21 is over-expressed in the majority of human malignancies including non-small cell lung cancer (NSCLC).
“MiR-21 is over-expressed in the majority of human malignancies including non-small cell lung cancer (NSCLC).”
The paper relies on this without support.
It is not clear whether miR-21 determines important aspects of lung cancer pathogenesis or is instead simply a marker for advanced disease.
“However, it is not clear whether miR-21 determines important aspects of lung cancer pathogenesis or is instead simply a marker for advanced disease.”
The paper relies on this without support.
Spry1, Spry2, Btg2, and Pdcd4 act as negative regulators of the Ras/MEK/ERK pathway.
“which act as negative regulators of the Ras/MEK/ERK pathway”
The paper relies on this without support.
Apaf1, Faslg, Pdcd4 and RhoB promote apoptosis.
“which promote apoptosis”
Citations
Cites
Bartel (2004) · doi:10.1016/s0092-8674(04)00045-5 · Cited by 34,714
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“Expression of approximately 30% of human proteins appears to be regulated by miRNAs (Lewis et al., 2005).”
MicroRNA signatures in human cancers
Calin, G. A., & Croce, C. M. (2006) · Nature reviews. Cancer · doi:10.1038/nrc1997 · Cited by 7,668 · cited 2×
“…including non-small-cell lung cancer (NSCLC) (Volinia et al., 2006), and are predictive of tumor classification, prognosis, and response to therapy (Calin and Croce, 2006). miRNA expression patterns are remarkably reliable markers of cancers; in some cases, they have even proven more reliable than…”
Oncomirs—MicroRNAs with a role in cancer
Esquela-Kerscher, A., & Slack, F. J. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1840 · Cited by 5,884 · cited 4×
“MicroRNAs are evolutionarily conserved, endogenous, nonprotein-coding, 20–23 nucleotide single-stranded RNAs that negatively regulate gene expression in a sequence-specific manner (Cho, 2007; Esquela-Kerscher and Slack, 2006; Voorhoeve and Agami, 2007).”
InfluentialA microRNA expression signature of human solid tumors defines cancer gene targets
Volinia, S., Calin, G. A., Liu, C.-G., Ambs, S., Cimmino, A., Petrocca, F., Visone, R., Iorio, M., Roldo, C., Ferracin, M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510565103 · Cited by 5,697 · cited 4×
“A large-scale survey to determine the miRNA signature of 540 tumor samples—including lung, breast, stomach, prostate, colon, and pancreatic tumors and their respective normal adjacent tissue—revealed miR-21 was the only miRNA upregulated in all these tumors (Volinia et al., 2006).”
InfluentialCombinatorial microRNA target predictions
Krek, A., Grün, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1536 · Cited by 4,603 · cited 2×
“, 2007), and PicTar (Krek et al., 2005).”
Silencing of microRNAs in vivo with ‘antagomirs’
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“Methods have been developed to manipulate miRNA function pharmacologically, facilitating the development of new cancer therapeutic strategies (Hutvagner et al., 2004; Krutzfeldt et al., 2005).”
MicroRNA Targeting Specificity in Mammals: Determinants beyond Seed Pairing
Grimson, A., Farh, K. K.-H., Johnston, W. K., Garrett-Engele, P., Lim, L. P., & Bartel, D. P. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.06.017 · Cited by 3,766 · cited 2×
“Can miR-21 Targets Multiple Tumor Suppressor Genes To identify miR-21 effectors responsible for phenotypes observed, we utilized two algorithms that predict the mRNA targets of miRNAs, TargetScan (Grimson et al., 2007), and PicTar (Krek et al.”
The impact of microRNAs on protein output
Baek, D., Villén, J., Shin, C., Camargo, F. D., Gygi, S. P., & Bartel, D. P. (2008) · Nature · doi:10.1038/nature07242 · Cited by 3,592 · cited 2×
“Through interactions with 30 UTRs, miRNAs can modulate the expression of many genes simultaneously, often regulating individual signaling pathways at multiple levels (Baek et al., 2008; Selbach et al., 2008).”
Widespread changes in protein synthesis induced by microRNAs
Selbach, M., Schwanhäusser, B., Thierfelder, N., Fang, Z., Khanin, R., & Rajewsky, N. (2008) · Nature · doi:10.1038/nature07228 · Cited by 3,429 · cited 2×
“Through interactions with 30 UTRs, miRNAs can modulate the expression of many genes simultaneously, often regulating individual signaling pathways at multiple levels (Baek et al., 2008; Selbach et al., 2008).”
Flagged first, then by citations
4 of the 74 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
MicroRNA therapeutics: towards a new era for the management of cancer and other diseases
Rupaimoole, R., & Slack, F. J. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2016.246 · Cited by 4,741
The role of MicroRNAs in human cancer
Peng, Y., & Croce, C. M. (2016) · Signal Transduction and Targeted Therapy · doi:10.1038/sigtrans.2015.4 · Cited by 2,566
The role of non-coding RNAs in oncology
Slack, F. J., & Chinnaiyan, A. M. (2019) · Cell · doi:10.1016/j.cell.2019.10.017 · Cited by 1,619
Leva, G. D., Garofalo, M., & Croce, C. M. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012513-104715 · Cited by 1,705
“Genetic deletion of miR-21 reduced lung tumor burden following activation of a mutant KrasG12D allele, and correspondingly, a miR-21 transgene increased tumor outgrowth (78).”
BackgroundMicroRNAs in Stress Signaling and Human Disease
Mendell, J. T., & Olson, E. N. (2012) · Cell · doi:10.1016/j.cell.2012.02.005 · Cited by 1,673
“Other miRNAs that appear to participate in similar positive feedback pathways to stably enforce oncogenic signaling programs include miR-21, which is activated by MAPK/ERK signaling and represses negative regulators of this signaling cascade (Hatley et al., 2010), and the miR-143/145 cluster, which is repressed when i…”
BackgroundSelf-citation
Metadata
- Authors
- Hatley, M. E., Patrick, D. M., Garcia, M. R., Richardson, J. A., Bassel-Duby, R., van Rooij, E., & Olson, E. N.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Olson, Eric N.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 18
- Issue
- 3
- Pages
- 282-293
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2971666
- OpenAlex
- W2169354377
- Semantic Scholar
- ea1aaa83b1883a1290ce31db3401b12568b668c7
- Cited by
- 626
- References
- 74
- Citations by year
- 2026: 12 · 2025: 15 · 2024: 26 · 2023: 22 · 2022: 38 · 2021: 31 · 2020: 28 · 2019: 29 · 2018: 42 · 2017: 31 · 2016: 40 · 2015: 72 · 2014: 57 · 2013: 62 · 2012: 63
- FWCI
- 16.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL093039)
- National Cancer Institute
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12HD000850)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Keywords
- miR-21, KRAS, lung carcinogenesis, non-small cell lung cancer, Ras/MEK/ERK pathway, apoptosis inhibition, transgenic mouse model, tumor suppressor microRNA
- MeSH terms
- Animals, Carcinoma, Non-Small-Cell Lung, Cell Transformation, Neoplastic, Humans, Lung Neoplasms, Mice, Nude, Mice, Transgenic, Genes, ras, Signal Transduction, MicroRNAs, Cell Line, Tumor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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