The DOI matches its Crossref record; 63 of the 64 references it cites were found in a registry or an index, and 1 are not checked yet; 15 of the 51 sources its claims cite were checked for support.
MicroRNA 21 Promotes Glioma Invasion by Targeting Matrix Metalloproteinase Regulators
Open accessAbstract
Substantial data indicate that microRNA 21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins. This microRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis, and migration. We demonstrate that miR-21 regulates multiple genes associated with glioma cell apoptosis, migration, and invasiveness, including the RECK and TIMP3 genes, which are suppressors of malignancy and inhibitors of matrix metalloproteinases (MMPs). Specific inhibition of miR-21 with antisense oligonucleotides leads to elevated levels of RECK and TIMP3 and therefore reduces MMP activities in vitro and in a human model of gliomas in nude mice. Moreover, downregulation of miR-21 in glioma cells leads to decreases of their migratory and invasion abilities. Our data suggest that miR-21 contributes to glioma malignancy by downregulation of MMP inhibitors, which leads to activation of MMPs, thus promoting invasiveness of cancer cells. Our results also indicate that inhibition of a single oncomir, like miR-21, with specific antisense molecules can provide a novel therapeutic approach for "physiological" modulation of multiple proteins whose expression is deregulated in cancer.
Verified 2026-10-19 · 1 reference not checked yet
Overview
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Written from the paper’s full text.
TL;DR
miR-21 is elevated in high-grade gliomas and promotes glioma invasion by directly targeting the MMP inhibitor RECK and indirectly regulating TIMP3, leading to increased MMP activity. Inhibiting miR-21 raises RECK/TIMP3, reduces MMP activity in vitro and in vivo, and decreases glioma cell motility and invasion, partly rescued by RECK knockdown.
Key findings
- miR-21 levels remain low in grade II gliomas and most grade III tumors but are significantly higher in GBMs; RECK mRNA is significantly lower in GBMs than normal brain and grade II/III gliomas, and TIMP3 mRNA tends to be lower in GBMs.
- Anti-miR-21 treatment changed expression of ∼570 genes (P < 0.05); upregulated transcripts were enriched for miR-21 seed hexamers (expectations 1.45e−09, 1.37e−14, and 1.82e−12), and at least 65 mRNAs were upregulated by anti-miR-21 and downregulated by miR-21 overexpression.
- miR-21 inhibition increased RECK mRNA ∼2-fold and TIMP3 mRNA about 1.6-fold; RECK was validated as a direct miR-21 target by luciferase reporter, whereas TIMP3 was not consistently directly responsive and is likely downstream.
- miR-21 inhibition reduced MMP-2 activity in A172 and U87 cells and lowered MMP activity in U87 subcutaneous tumors in nude mice; it also reduced scratch motility and Matrigel invasion, with reduced motility partly rescued by RECK siRNA and reduced invasion not observed when anti-miR-21 was cotransfected with RECK siRNA.
Methods
- Human glioma cell lines A172, U87, and LN229 (high miR-21), plus HeLa, MCF7, and U2OS cells, and human nonneoplastic brain and tumor samples; cells were transfected with 2′-O-MOE anti-miR-21, mismatch/control oligonucleotides, synthetic miR-21 duplex, or RECK siRNA.
- mRNA profiling used Agilent 44K arrays at 6 and 24 h posttreatment, with qRT-PCR, Western blot, luciferase 3′ UTR reporter assays with mutated miR-21 binding sites, gelatin zymography, scratch migration, and Matrigel invasion assays.
- In vivo, U87 cells transfected with anti-miR-21 or control were implanted subcutaneously in nude mice; MMP activity was imaged with MMPSense 680 at 3 days after implantation and 24 h later, with caliper tumor measurements.
Limitations
- Stated by the authors: the 2′-O-MOE anti-miR-21 did not significantly or consistently change glioma cell viability or reduce subcutaneous U87 tumor growth; subcutaneous U87 tumors are noninfiltrative, noninvasive, and poorly vascularized, so they are not an accurate model for studying invasiveness and tumor growth; nucleic acid chemistry can profoundly alter cellular responses to miRNA inhibition; therapeutic potential requires future research.
- Stated/evident from the text: the TIMP3 3′ UTR reporter did not consistently respond to miR-21 changes, so TIMP3 is likely a downstream effector rather than a direct target; RECK protein bands were not detectable by Western blot in U87 cells despite ∼2-fold RECK mRNA upregulation.
- Evident from the text: in vivo imaging was performed within the first week, when anti-miR-21 did not affect subcutaneous U87 tumor growth; comparison with a prior intracranial LNA-DNA anti-miR-21 study is limited because tumor locations differed.
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Claims the paper makes
35 Own result · 20 Own interpretation · 18 No full text of the sources · 6 Supported · 6 Own method · 4 Supported so far · 4 Partly supported · 2 No basis given · accuracy not yet measured
Every source the paper cites for this claim was checked and supports it.
In the paper
“Among the molecules tested, the 2′-O-MOE ASO was the most potent in repressing miR-21 activity (Fig. 2A), in agreement with previous data (10), whereas the uniform 2′-O-methyl ASO was the least potent, and mixed locked nucleic acid (LNA)-DNA oligonucleotides were variable (data not shown).”
What the sources say
- Supportedcites [10] source
The Discussion explicitly identifies the uniformly modified 2′-O-MOE-PO oligonucleotide as the best anti-miRNA ASO tested. This supports the attributed comparison for miR-21 activity, although the passage specifies the oligonucleotide’s backbone as PO. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- 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
“Concurring with previously published reports (12, 46), our data indicate that these MMP inhibitors regulate MMP activity posttranslationally.”
What the sources say
- Supportedcites [12] source
The paper describes TIMPs as inhibitors of metalloproteinase activity and shows that TIMP-3 controls the cell-surface activation of pro-MMP-2 (Abstract and Discussion; page numbers unavailable). Its gene-expression analysis found comparable MMP-2 levels in wild-type and TIMP-3-deficient cells despite altered processing, supporting regulation after translation. (LLM, conf=0.91)
- Not checked — no full text of the sourcecites [46] source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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- Rests on an assumption: MMPs are a group of peptidases involved in degradation of the ECM.
- Supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“However, we have not detected any correlation between miR-21-modulated expression in several glioma cell lines and protein level of phosphatase and tensin homolog (data not shown), the reported miR-21 target in hepatocellular carcinomas (44).”
What the sources say
- Supportedcites [44] source
The citation supports the identification of PTEN as a reported miR-21 target in hepatocellular carcinoma: the Results state that PTEN was shown to be a direct target of miR-21 in HCC cells. The preceding statement about no correlation in glioma cell lines is the citing authors’ own unpublished observation, not a finding attributed to this source. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Our data suggest that this can be at least partly due to miR-21 regulation, in addition to the reported chromosome 12q22-23 loss of heterozygosity and hypermethylation (56).”
What the sources say
- Partly supportedcites [56] Watanabe T., 2003, Brain Pathol. sourceExperimental — accuracy not yet measured
The Abstract (page unavailable) reports chromosome 12q22–23 loss of heterozygosity in glioblastomas and its association with low Apaf-1 expression. It mentions hypermethylation only as a possible mechanism in some malignancies; the reported study did not measure it in glioblastomas. The miR-21 proposal is presented as the citing authors’ own conclusion, not as a finding attributed to this source. (LLM, conf=0.83)
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In gliomas, APAF1 is often inactivated or downregulated (56).”
What the sources say
- Partly supportedcites [56] Watanabe T., 2003, Brain Pathol. sourceExperimental — accuracy not yet measured
The Abstract reports low APAF1 mRNA and protein expression in many glioblastomas with chromosome 12q22–23 loss of heterozygosity. The study examined glioblastoma, however, so it does not establish that APAF1 is often inactivated or downregulated across gliomas generally. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
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- 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
“The numbers of invasive A172 and U87 cells in cultures with inhibited miR-21 were significantly reduced relative to those in cultures transfected with the control oligonucleotide (Fig. 7A and B).”
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“Specific inhibition of miR-21 with antisense oligonucleotides leads to elevated levels of RECK and TIMP3 and therefore reduces MMP activities in vitro and in a human model of gliomas in nude mice.”
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“Moreover, downregulation of miR-21 in glioma cells leads to decreases of their migratory and invasion abilities.”
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“RECK mRNA expression was significantly lower in GBMs than in normal brain tissue and, especially, in grade II and III gliomas.”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“When miR-21 was suppressed, the amount of gelatin digested that reflects the levels of MMP-2 proteolytic activity was significantly reduced relative to the amount for the cells transfected with the control oligonucleotide (Fig. 5A).”
plaindirect- Asserted: passes — The authors put it forward as true.
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- It may state two separate claims as one. 28
- Probably not a substantial claim. 21
- The quote only partly states this claim. 2
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Accumulated data suggested that MMP levels and activities are significantly elevated in human gliomas, which contributes to glioma cell invasion of the surrounding normal tissues, metastasis, and angiogenesis through cell surface ECM degradation (21, 45).”
What the sources say
- Not checked — no full text of the sourcecites [21] Hu B., 2003, Proc. Natl. Acad. Sci. USA source
- Partly supportedcites [45] sourceExperimental — accuracy not yet measured
The Abstract and §4.1 link elevated MMP levels in human gliomas to invasiveness, and describe ECM degradation and cell-surface activation. But the Abstract discusses metastasis in cancer generally, not specifically gliomas; §4.2 links MMP-9 to angiogenesis only tentatively and says its activity in invasive glioma tissue is unproven. The copy therefore does not establish significantly elevated MMP activities across human gliomas or the claimed glioma metastasis and angiogenesis mechanism. Page numbers were not supplied. (LLM, conf=0.88)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: MMPs are a group of peptidases involved in degradation of the ECM.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“TIMP3 is a tissue inhibitor of MMPs that inhibits angiogenesis and tumor cell infiltration and also induces apoptosis (2, 48).”
What the sources say
- Partly supportedcites [2] sourceExperimental — accuracy not yet measured
The paper’s Summary (p. 1347) identifies TIMP-3 as a tissue inhibitor of metalloproteinases, and its discussion reports inhibited invasion of HeLa and HT1080 cancer cells and apoptotic death in three cancer cell lines. The copy does not report that TIMP-3 inhibits angiogenesis; searches for angiogenesis and blood-vessel formation found no supporting passage. (LLM, conf=0.88)
- Not checked — no full text of the sourcecites [48] source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
- 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
“This microRNA has been implicated in various aspects of carcinogenesis, including cellular proliferation, apoptosis, and migration.”
- Also stated in: § Abstract · plain
“miR-21 has been identified in controlling apoptosis, cell proliferation, and migration of cell lines in breast, colorectal, and other cancers (1, 44, 51, 59).”
What the sources say
- Not checked — no full text of the sourcecites [1] source
- Supportedcites [44] source
The Results report that changing miR-21 expression affects proliferation and migration in HCC cells. The Discussion also reports anti-apoptotic properties of miR-21 in glioblastoma and cholangiocarcinoma, supporting the broader statement that it has been implicated in all three processes. (LLM, conf=0.92)
- Not checked — no full text of the sourcecites [51] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Abstract · plain
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
“Our analysis also confirmed tropomyosin 1 (TPM1) regulation by miR-21, previously reported to occur in MCF7 cells (59, 60).”
What the sources say
- Supportedcites [59] source
The Abstract reports that experiments using tumors derived from MCF-7 cells identified TPM1 as a miR-21 target and confirmed that miR-21 down-regulates its expression. The Results section also reports increased endogenous TPM1 in anti-miR-21-treated, MCF-7-derived tumors. The paper therefore supports the cited prior report, although its tumor measurements were made in MCF-7-derived tumors rather than isolated cells. (LLM, conf=0.90)
- Not checked — no full text of the sourcecites [60] source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably 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
“Another factor that can induce miR-21 expression is hypoxia, a general feature of all solid tumors (30).”
What the sources say
- Supportedcites [30] source
The Results report miR-21 among the hypoxia-regulated microRNAs and say its microarray result was checked by quantitative RT-PCR. The introductory passage describes hypoxia as an essential feature of the neoplastic microenvironment. (LLM, conf=0.90)
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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Every source the paper cites for this claim was checked and supports it.
In the paper
“The miR-21 gene contains two conserved STAT3 binding sites within its enhancer region and is induced by interleukin 6 (IL-6) in a STAT3-dependent way.”
What the sources say
- Supportedcites [39] source
The Results and discussion section identifies two conserved Stat3 binding sites in the miR-21 upstream regulatory region. It also reports that IL-6 increased miR-21 expression and that Stat3 knockdown inhibited this induction. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably 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
“MMPs can degrade ECM components and therefore play important roles in mediating GBM tumor cell motility and invasion (45).”
What the sources say
- Supportedcites [45] source
The Introduction says MMPs can degrade nearly all ECM macromolecules in the brain and are believed to play a major role in tumor invasion. The Abstract links MMP-mediated ECM degradation to glioblastoma invasion, while Section 4 describes how ECM degradation may permit glioma-cell migration. (LLM, conf=0.92)
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“APAF1 (apoptotic protease activating factor 1) is the molecular core of apoptosome. It is typically required for activation of the caspases that initiate apoptosis (3, 26).”
What the sources say
- Supportedcites [3] source
The Introduction describes Apaf-1 oligomerization as forming the apoptosome, while the Results and discussion state that Apaf-1 normally recruits and activates caspases-9 and -3. The Concluding remarks add that caspase-9 activity depends on interaction with oligomerized Apaf-1. Page numbers are not provided in our copy. (LLM, conf=0.90)
- Supportedcites [26] Johnson C. E., 2007, Proc. Natl. Acad. Sci. USA source
The paper’s introductory discussion (page not specified in our copy) says cytochrome c binds Apaf-1, leading to recruitment of procaspase-9 and formation of the apoptosome; the apoptosome then activates caspase-9. In the section on Apaf-1 expression levels (page not specified), adding Apaf-1 enabled cytochrome c to activate caspases in neural extracts, supporting its required role in the pathway described. (LLM, conf=0.91)
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- 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
“Elevated miR-21 expression has been causally linked to proliferation, apoptosis, and migration of several cancer cell lines (1, 5, 44, 60).”
What the sources say
- Not checked — no full text of the sourcecites [1] source
- Not checked — no full text of the sourcecites [5] source
- Supportedcites [44] source
The Results report that experimentally increasing or inhibiting miR-21 changed proliferation and migration in HCC cell lines. The Discussion reports anti-apoptotic properties of miR-21 in glioblastoma and cholangiocarcinoma, supporting the apoptosis part as a finding the paper reports from other studies. (LLM, conf=0.87)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably 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
“miR-21 levels remain low in grade II gliomas and in most grade III tumors and are significantly higher in GBMs (Fig. 1).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“This expression pattern is different from those of the other cancer-associated miRNAs, for example, miR-10b, which is often elevated in grade III and even grade II gliomas (Fig. 1) and dysregulated in some other cancers (41).”
What the sources say
- Not checked — no full text of the sourcecites [41] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It 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
“RECK mRNA level increased consistently ∼2-fold and TIMP3 mRNA about 1.6-fold in the cells transfected with anti-miR-21.”
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
“These experiments demonstrated that inhibition of miR-21 reduced the motility of glioma cells (Fig. 6B and C).”
boosteddirect- Asserted: passes — The authors put it forward as true.
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The quote only partly states this claim.
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
“We note that, though 2′-O-MOE miR-21 ASO induced many proapoptotic and cell cycle arrest genes (Fig. 2C; also see Table S1 in the supplemental material), it did not significantly and consistently change the viability of glioma cell lines, which was reported for other, less potent miR-21 inhibitors (5, 8).”
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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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
“STAT3, the other gene that may play a tumor suppressor function in GBM (11), is also negatively regulated by miR-21 according to the microarray data (see Table S1 in the supplemental material) and is a predicted miR-21 target (29, 34).”
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
“As identified in our study, TIMP3 or both TIMP3 and RECK are also induced by anti-miR-21 in MCF7 (breast carcinoma) and U2OS (osteosarcoma) cells (Fig. 4D).”
plaindirect- Asserted: passes — The authors put it forward as true.
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It 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
“In glioma progression from less invasive grade II gliomas to very invasive GBMs, RECK and TIMP3 levels drop (Fig. 4B), whereas miR-21 expression increases (Fig. 1).”
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It 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
“Here, we show that a 2′-O-MOE ASO not only is potent but also upregulates miR-21 seed-containing mRNAs (Fig. 2 and 3).”
boosteddirect- Asserted: passes — The authors put it forward as true.
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It 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
“Substantial data indicate that microRNA 21 (miR-21) is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins.”
- Also stated in: § Abstract · boosted
“Using high-throughput profiling of miRNA expression, we have previously identified a specific miRNA, miRNA 21 (miR-21), as most strongly elevated in nearly all analyzed human GBM specimens (5).”
- Also stated in: § Abstract · boosted
“Other groups demonstrated overexpression of this miRNA in a wide range of other cancers, including breast, lung, colon, prostate, pancreas, ovarian, and stomach cancers, as well as in chronic lymphocytic leukemia (33, 54).”
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Abstract · boosted
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
“mRNAs carrying RECK and TIMP3 are predicted conserved miR-21 targets with one and two putative binding sites, respectively (Fig. 4A).”
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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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
“The sequences of the control and mismatch oligonucleotides have been analyzed using BLAST searches to exclude potential hits in the human transcriptome.”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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Probably 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
“RECK is a membrane-anchored MMP inhibitor whose reduced expression or inactivation seems to be critical for the invasiveness and metastasis of various cancers, including glioma cancer (7, 46).”
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“The high level of miR-21 expression in GBMs compared to that in anaplastic astrocytomas suggests the involvement of miR-21 in one of these key processes.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The quote only partly states this claim.
In the paper
“Its expression level is also an important prognostic factor for multiple cancer types (6).”
What the sources say
- Not checked — no full text of the sourcecites [6] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“It has been demonstrated to inhibit MMP activity and tumor growth in malignant gliomas in vivo (31, 32).”
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“Since modified oligonucleotides can induce a wide range of nonspecific, off-target-mediated effects, several ASO molecules of different chemistries have been used for miR-21 inhibition.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“Our data suggest that miR-21 contributes to glioma malignancy by downregulation of MMP inhibitors, which leads to activation of MMPs, thus promoting invasiveness of cancer cells.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: MMPs are a group of peptidases involved in degradation of the ECM.
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
“Such overrepresentation of the hexamers suggests an abundance of direct miR-21 targets among the genes upregulated by 2′-O-MOE anti-miR-21 and indicates that the effects of this molecule on glioma cells are indeed mediated through the miR-21 pathway.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“These experiments have been performed with the miR-21 inhibitor and with a mismatched control oligonucleotide to ensure that any observed effects are driven by miR-21.”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“Importantly, it inhibits tumor necrosis factor alpha-converting enzyme and induces apoptosis through the stabilization of tumor necrosis factor alpha receptors on the cell surface (42).”
What the sources say
- Not checked — no full text of the sourcecites [42] source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“Moreover, it leads to reduction of glioma cell motility and invasion, which is mediated by elevated RECK expression and was partly rescued by RECK siRNA (Fig. 6 and 7).”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“This implies that miR-21 regulates RECK and TIMP3 expression and thus MMP activities and glioma tumor invasiveness.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“In this study, we have demonstrated in vitro and in vivo, using U87 glioma xenografts in nude mice, that miR-21 regulates MMPs and glioma cell invasiveness by directly controlling the MMP inhibitor RECK.”
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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
“These combined results indicate that miR-21 regulates overlapping though not identical sets of genes in different cells and therefore shares common signaling pathways in different cancers.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“The APAF1 3′ UTR contains a strong miR-21 binding site (9-mer binding at miR-21 5′ end), and therefore, it is likely one of the direct miR-21 targets.”
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It 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
“Its expression is highly upregulated in a variety of solid tumors, including GBM, breast, lung, colon, prostate, pancreas, and stomach cancers (5, 54).”
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“Our mRNA expression analysis suggests that miR-21 regulates the expression of multiple mRNA targets and thereby induces several cellular programs in glioma cells, including those associated with the tumor invasiveness and microvascular proliferation typical for the GBM as well as those involved in cell cycle regulation and apoptosis.”
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Its ectopic expression in glioma cells induces upregulation of genes associated with angiogenesis, growth factors, cytokines, death receptors, and substrates of the various MMPs (31).”
What the sources say
- Not checked — no full text of the sourcecites [31] Lam P., 2005, Mol. Ther. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“RECK, a membrane-anchored regulator, and TIMP3, the ECM-bound protease regulator, are key inhibitors of several MMPs, and their expression is prognostic in a number of common cancers (28, 53).”
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It 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
“TIMP3 has been demonstrated to activate caspases and therefore induce apoptosis of human glioma cells in vitro and the growth inhibition of human glioma tumors in a mouse model (31, 32).”
What the sources say
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably 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
“Though mRNA expression analysis does not allow identification of targets whose translation is regulated without modulation of mRNA levels”
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
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
“Such a bidirectional approach to manipulating miR-21 levels enabled narrowing of the lists of regulated genes and identification of those whose expression correlated negatively with miR-21 levels”
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In these experiments, we used tumorigenic U87 cells, a common model of human gliomas (23).”
What the sources say
- Not checked — no full text of the sourcecites [23] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
MMPs are a group of peptidases involved in degradation of the ECM.
“MMPs are a group of peptidases involved in degradation of the ECM.”
The paper relies on this without support.
Subcutaneous U87 tumors are noninfiltrative, noninvasive, and poorly vascularized.
“We should also note that subcutaneous U87 tumors are noninfiltrative, noninvasive, and poorly vascularized.”
The paper relies on this without support.
Knowledge of the molecular mechanisms mediating miR-21 function in cancer generally and in gliomas specifically is limited.
“However, our knowledge of the molecular mechanisms mediating miR-21 function in cancer generally and gliomas specifically is limited.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“miR-21 is a well-known miRNA, found to be overexpressed in almost all cancer types, where its upregulation promotes cell proliferation, invasion, and metastatic behavior.”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Previous studies have proven that PDCD4, HNRNPK and RECK are TSGs among the direct targets of miR-21-5p (13,(27)(28)(29).”
From Functional interaction between miR-505-3p and miR-21 contributes to GBM suppression (2026) · cites this paper as [28]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“miR-21 targets several genes such as PDCD4, TIMP3, and RECK, which are key regulators of apoptotic and metastatic pathways (17–23).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Our data on the effects of miR-21 enriched exosomes is in agreement with the previous reports demonstrating that overexpressed miR-21 in cell lines can increase the proliferation rate and malignant behavior of the cells (17–23).”
From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [17]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ DISCUSSION
“Its overexpression by viral transduction induces apoptosis in glioma cells and may be beneficial in glioma treatment (50).”
§ REFERENCES
“50.Shinoura, N., N. Yamamoto, Y. Yoshida, A. Asai, T. Kirino, and H. Hamada. 2000. Adenovirus-mediated transfer of caspase-8 in combination with superrepressor of NF-kappaB drastically induced apoptosis in gliomas.”
Citations
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“…is known to be highly upregulated in malignant gliomas and is known to contribute to tumor’s resistance to chemotherapy and radiotherapy by targeting many tumor suppressor genes like PTEN, PDCD4, FOXO1, and TAP63 (Gabriely et al. 2008; Krichevsky and Gabriely 2009; Papagiannakopoulos et al. 2008).”
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“Moreover, miR-21 also promotes glioblastoma invasiveness through suppression of the expression of matrix metalloprotease (MMP) inhibitors, such as TIMP3 and RECK [68].”
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“Additionally, in recent years, there has been much experimental evidence that the reversion-inducing-cysteine-rich protein with kazal motifs (RECK) could reduce the metastasis and invasion of various cancer cells, including malignant glioma [27,28], through regulating matrix metalloproteinases (MMPs) [29] and associat…”
BackgroundNasirian, V., Shamsipur, M., Molaabasi, F., Mansouri, K., Sarparast, M., Salim, V., Barati, A., & Kashanian, S. (2020) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2020.127673 · Cited by 27
Circulating microRNAs for Early Diagnosis of Ovarian Cancer: A Systematic Review and Meta-Analysis
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“In terms of glioma, MMP-2 and MMP-9 could be regulated by microRNA-21 as well as specificity protein 1 (Sp1) in human glioma, thus contributing to glioma cell invasiveness.(25,26) Recently, GPNMB was reported to be capable of increasing the invasion capacity of metastatic prostate cancer cells by regulating the MMP-2/…”
BackgroundA Comprehensive Review of Genomics and Noncoding RNA in Gliomas
Hassan, A. M., Mosley, J. C., Singh, S. K., & Zinn, P. O. (2017) · Topics in Magnetic Resonance Imaging · doi:10.1097/rmr.0000000000000111 · Cited by 28
“Thus, miR-21 promotes glioma malignancy by downregulating MMP inhibitors, which leads to activation of MMPs and induction of invasion.(116)”
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MicroRNA‐21 drives the switch to a synthetic phenotype in human saphenous vein smooth muscle cells
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“Furthermore, this study confirmed direct regulation of RECK but not TIMP3 by miR-21 via luciferase assay, suggesting that TIMP3 may be an indirect target of miR-21 or that it serves as a downstream effector [23].”
BackgroundMicroRNAs as Multifaceted Players in Glioblastoma Multiforme
Mercatelli, N., Galardi, S., & Ciafrè, S. A. (2017) · International review of cytology · doi:10.1016/bs.ircmb.2017.03.002 · Cited by 27
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“TIMP3 has shown to be a miR-21 gene target [23, 48, 58].”
BackgroundUse of microRNAs as Diagnostic, Prognostic, and Therapeutic Tools for Glioblastoma
Valle‐García, D., de la Cruz, V. P., Flores, I., Salazar, A., Pineda, B., & Meza‐Sosa, K. F. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25052464 · Cited by 26
“…as the insulin-like growth factor (IGF)-binding protein-3 ( IGFBP3 ) [58], re-version inducing cysteine-rich protein with kazal motifs ( RECK ) [59], and TIMP metallo-peptidase inhibitor 3 ( TIMP3 ) [59], resulting in enhanced cell migration and invasiveness and reduced apoptosis of tumor…”
BackgroundReducible Micelleplexes are Stable Systems for Anti-miRNA Delivery in Cerebrospinal Fluid
Zhang, Y., Buhrman, J. S., Liu, Y., Rayahin, J., & Gemeinhart, R. A. (2016) · Molecular Pharmaceutics · doi:10.1021/acs.molpharmaceut.5b00933 · Cited by 26
Modulation of miR-21 signaling by MPS1 in human glioblastoma
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“Substantial data indicate that miR-21 is significantly elevated in glioblastoma (GBM) and in many other tumors of various origins [43-46].”
BackgroundMicroarray-based analysis of gene regulation by transcription factors and microRNAs in glioma
Yu, J., Cai, X., He, J.-Q., et al. (2012) · Neurological Sciences · doi:10.1007/s10072-012-1228-1 · Cited by 24
MicroRNA-mediated gene regulations in human sarcomas
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“For instance, over 40 miRNAs are implicated in cellular apoptosis [36] and some may have overlapping roles in other cancer mechanisms such as cell angiogenesis, invasion and metastasis [37–39].”
BackgroundEpigenetics of Neurological Cancers
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“Knockdown of miR-21 leads to repression of cell growth, increased apoptosis, and cell-cycle arrest, as well as decreased ability to migrate and invade [101,102].”
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Methylation of the miR-126 gene associated with glioma progression
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Potential role of miRNAs and their inhibitors in glioma treatment
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“Interestingly, although there is increased expression of both cytoplasmic HuR and miR-21 in primary Glioblastoma cells [27, 35-37], the expression of PDCD4 in these cells is reduced.”
BackgroundmiR-21: a promising biomarker for the early detection of colon cancer
Dehghan, F., Boozarpour, S., Torabizadeh, Z., & Alijanpour, S. (2019) · OncoTargets and Therapy · doi:10.2147/ott.s199508 · Cited by 23
Systematic Review of MicroRNAs and its Therapeutic Potential in Glioma
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miR-214 down-regulates MKK3 and suppresses malignant phenotypes of cervical cancer cells
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Genomic, epigenomic and transcriptomic landscape of glioblastoma
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“Additionally, low levels of miR-21 in human malignan - cies have been found to be related to a slightly improved survival rate, while high levels of miR-148a expression is linked to longer survival, as reported by the TCGA data - base (Gabriely et al. 2008; Kim et al. 2014; Malzkorn et al. 2010 ).”
A MicroRNA Component of the Neoplastic Microenvironment: Microregulators with Far-Reaching Impact
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“Mechanistically, several studies have shown that the expression level of miR-21 is inversely correlated with that of two MMP inhibitors, RECK and TIMP3, which are suppressors of malignancy [12, 17].”
BackgroundThe potential of RECK inducers as antitumor agents for glioma.
Chen, Y., & Tseng, S. (2012) · PubMed · Cited by 22
MicroRNAs and other mechanisms regulate interleukin-17 cytokines and receptors
Mai, J. (2011) · Frontiers in Bioscience-Elite · doi:10.2741/474 · Cited by 19
MicroRNA-21 contributes to the discrimination of chemoresistance in metastatic gastric cancer
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miR‑218 inhibits the proliferation of human glioma cells through downregulation of Yin Yang 1
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“miRNAs regulate a wide variety of biological processes including cell migration, invasion, proliferation, apoptosis, tumorigenesis and tissue morphogenesis (5-8).”
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Prospects for miR-21 as a Target in the Treatment of Lung Diseases
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Pediatric eosinophilic esophagitis is associated with changes in esophageal microRNAs
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“Transcripts targeted by miR-21, including transforming growth factor- 1 and suppressor of cytokine signaling 5, may play an important role in pediatric EoE pathogenesis (12, 14, 27).”
BackgroundMiRNAs as Biomarkers for Management of Patients With Colorectal Cancer
Manne, U., Shanmugam, C., Bovell, L. C., Katkoori, V. R., & Bumpers, H. L. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.10.87 · Cited by 22
Stromal Expression of MicroRNA-21 in Advanced Colorectal Cancer Patients with Distant Metastases
Lee, K. S., Nam, S. K., Koh, J., Kim, D., Kang, S., Choe, G., Kim, W. H., & Lee, H. S. (2016) · Journal of Pathology and Translational Medicine · doi:10.4132/jptm.2016.03.19 · Cited by 22
“Recent research on HNSCC conducted by Zhang et al.5 showed that parafibromin expression was negatively correlated with lymph node metastasis and TNM staging but positively correlated with human papillomavirus positivity.”
BackgroundMethodInfluentialWei, Y., Sun, J., & Li, X. (2016) · Biotechnology Letters · doi:10.1007/s10529-016-2251-8 · Cited by 21
“In glioma analysis, many miRNAs, including miR-215 (Tong et al. 2015), miR-21 (Gabriely et al. 2008) and miR218 (Tu et al. 2013), are dysregulated.”
BackgroundRetractedMicroRNAs in Rectal Cancer: Functional Significance and Promising Therapeutic Value
Imedio, L., Cristóbal, I., Rubio, J., Santos, A., Rojo, F., & García‐Foncillas, J. (2020) · Cancers · doi:10.3390/cancers12082040 · Cited by 21
“discovered a negative regulation of miR-21 on RECK and TIMP3 genes, which are inhibitors of MMPs [40].”
BackgroundInfluentialHuang, W., Shi, Y., Han, B., et al. (2019) · Cell Biochemistry and Function · doi:10.1002/cbf.3451 · Cited by 20
“For instance, Gabriely et al demonstrated that overexpression of miR‐21 promoted glioma cells invasion by decreasing MMP regulators.(13) Increased miR‐128 level significantly restrained glioma cells proliferation via regulating E2F3a.”
BackgroundReyes-Long, S., Cortes-Altamirano, J. L., Bandala, C., Avendaño-Ortiz, K., Bonilla‐Jaime, H., Bueno-Nava, A., Ávila-Luna, A., Sánchez-Aparicio, P., Clavijo‐Cornejo, D., Dotor-Llerena, A. L., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043574 · Cited by 20
MiR-21 Regulates Growth and Migration of Cervical Cancer Cells by RECK Signaling Pathway
Aguilar-Martínez, S. Y., Campos-Viguri, G. E., Medina-García, S. E., García-Flores, R. J., Deas, J., Gómez-Cerón, C., Pedroza‐Torres, A., Bautista, E., Fernández‐Tilapa, G., Rodríguez‐Dorantes, M., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25074086 · Cited by 25
“For instance, it has been reported that the overexpression of miR-21 negatively regulates RECK gene expression in glioma [38,39], nerve injury [40], osteosarcoma [41], esophageal squamous cell carcinoma [42], and colon cancer [43].”
BackgroundCharacterization of Human Osteoarthritic Cartilage Using Optical and Magnetic Resonance Imaging
Jones, E. F., Schooler, J., Miller, D. C., Drake, C. R., Wahnishe, H., Siddiqui, S. M., Li, X., & Majumdar, S. (2011) · Molecular Imaging and Biology · doi:10.1007/s11307-011-0480-8 · Cited by 19
“While MMPSense continues to demonstrate its ability to detect and define MMP activities in the tumor microenvironment [31–33] and rheumatoid arthritis [34], the utility of this probe for the characterization of OA is under explored.”
BackgroundSchmitz, U., Naderi‐Meshkin, H., Gupta, S. K., Wolkenhauer, O., & Vera, J. (2015) · Briefings in Bioinformatics · doi:10.1093/bib/bbv061 · Cited by 20
miR-21-3p Targets Elovl5 and Regulates Triglyceride Production in Mammary Epithelial Cells of Cow
Li, X., Jiang, P., Yu, H., Yang, Y., Xia, L., Yang, R., Fang, X., & Zhao, Z. (2019) · DNA and Cell Biology · doi:10.1089/dna.2018.4409 · Cited by 20
“It has been reported that miRNA-21 may be involved in a variety of regulatory pathways including p53, TGF-b , and mitochondrial apoptosis (Gabriely et al. , 2008). miRNA microarray analysis revealed that miR-21 expression was increased after berberine treatment in HepG2 human hepatoma cell lines,…”
Xu, F., Xu, L., Wang, M., An, G., & Feng, G. (2015) · Colorectal Disease · doi:10.1111/codi.12917 · Cited by 20
c-Fos/microRNA-18a feedback loop modulates the tumor growth via HMBOX1 in human gliomas
Zhou, J., Wang, M., & Deng, D. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.08.157 · Cited by 20
Hasani, F., Masrour, M., Jazi, K., Ahmadi, P., Hosseini, S. S., Lu, V. M., & Alborzi, A. M. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1357321 · Cited by 23
“…miRNA-21, showed the lowest concentrations in grade I and II tumors, increasing by reaching higher grades peaking The progression-free survival hazard ratios meta-analysis. in GBM samples (24, 64–67). miRNA-128, known as a tumor suppressor and an favorable diagnostic biomarker in glioma (67, 68).”
BackgroundMunthe, S., Halle, B., Boldt, H. B., et al. (2017) · Journal of Neuro-Oncology · doi:10.1007/s11060-016-2356-x · Cited by 19
“In that study, a miR-32 containing construct was transfected into the commercial cell line U87MG and orthotopic in vivo experiments revealed a significantly reduced tumor volume as well as prolonged survival upon overexpression.”
ResultSmall RNA and its application in andrology and urology.
Wang, J., & Li, L. C. (2012) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2223-4683.2011.12.04 · Cited by 18
“OncomiRs miR-17-92 PTEN, BIM, TSP1 and CTGF (15),(16) miR-106b-25 BIM, p21, PTEN and p53 (17),(18),(19) miR-221/222 p27, p57, DDIT4, PTEN and TIMP3 (20),(21),(22) miR-21 PDCD4, PTEN, RHOB, RECK and TIMP3 (23),(24),(25),(26)”
InfluentialCirculating Biomarkers of CNS Tumors: An Update
Ilhan‐Mutlu, A., Wagner, L., & Preusser, M. (2013) · Biomarkers in Medicine · doi:10.2217/bmm.13.12 · Cited by 19
Isolation and characterization of novelRECKtumor suppressor gene splice variants
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Density- and serum-dependent regulation of the Reck tumor suppressor in mouse embryo fibroblasts
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Micromanaging microRNAs: using murine models to study microRNAs in lung fibrosis
Cardenas, C. L. L., Kaminski, N., & Kass, D. J. (2013) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2012.11.003 · Cited by 19
“RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and TIMP3 (tissue inhibitor of metalloproteinases 3) [26].”
BackgroundTian, X., & Zhang, X. (2016) · Cellular Physiology and Biochemistry · doi:10.1159/000443084 · Cited by 18
Regulation of microRNA ‐21 expression by natural products in cancer
Shakeri, A., Ghanbari, M., Tasbandi, A., & Sahebkar, A. (2021) · Phytotherapy Research · doi:10.1002/ptr.7069 · Cited by 19
“Furthermore, miR-21 targets p53, TGF-β, and apoptotic mitochondrial factors to reduce apoptosis and to improve tumor cell migration via suppressing RECK and TIMP3 and MMP regulators in glioblastoma cells (Gabriely et al., 2008; Papagiannakopoulos et al., 2008).”
BackgroundThe bone marrow metastasis niche in retinoblastoma
Khosravi, A., Shahrabi, S., Shahjahani, M., & Saki, N. (2015) · Cellular Oncology · doi:10.1007/s13402-015-0232-x · Cited by 18
Stem Cells in Brain Tumor Development
Llaguno, S. R. A., Chen, Y., McKay, R. M., & Parada, L. F. (2011) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/b978-0-12-380916-2.00002-4 · Cited by 18
Metadata
- Authors
- Gabriely, G., Wurdinger, T., Kesari, S., Esau, C. C., Burchard, J., Linsley, P. S., & Krichevsky, A. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Regulus Therapeutics (United States) (US)
- Corresponding author
- Krichevsky, Anna M.
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2008-09-01
- Volume
- 28
- Issue
- 17
- Pages
- 5369-5380
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC2519720
- OpenAlex
- W2163655902
- Cited by
- 888
- References
- 62
- Citations by year
- 2026: 13 · 2025: 19 · 2024: 21 · 2023: 29 · 2022: 20 · 2021: 21 · 2020: 43 · 2019: 41 · 2018: 33 · 2017: 56 · 2016: 56 · 2015: 75 · 2014: 76 · 2013: 86 · 2012: 91
- FWCI
- 21.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- PubMed Central (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- National Institutes of Health (CA86355)
- National Cancer Institute (R21 CA116141, P50 CA86355-04, P50CA086355)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Oncology › Glioma Diagnosis and Treatment
- Keywords
- miR-21, glioma invasion, glioblastoma, matrix metalloproteinases, RECK, TIMP-3, matrix metalloproteinase inhibitors, cell migration, apoptosis, antisense oligonucleotides, microRNA inhibition, tumor malignancy
- MeSH terms
- Animals, Base Sequence, Cell Movement, Enzyme Inhibitors, Extracellular Matrix, Glioma, Humans, Molecular Sequence Data, Neoplasm Invasiveness, Neoplasm Transplantation, RNA, Messenger, Down-Regulation, Gene Expression Regulation, Neoplastic, Apoptosis, Disease Progression, Oligonucleotide Array Sequence Analysis, Matrix Metalloproteinases, Gene Expression Profiling, MicroRNAs, Cell Line, Tumor, Mice, Genes, Neoplasm, Matrix Metalloproteinase Inhibitors
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