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Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo
Open accessAbstract
MicroRNAs (miRNAs) are small, noncoding RNAs that play a critical role in developmental and physiological processes and are implicated in the pathogenesis of several human diseases, including cancer. They function by regulating target gene expression post-transcriptionally. In this study, we examined the role of oncogenic mir-21 in the pathogenesis of glioblastoma, the most aggressive form of primary brain tumor. We have previously reported that mir-21 is expressed at higher levels in primary glioblastoma-tissue and glioblastoma-derived cell lines than in normal brain tissue. We demonstrate that downregulation of mir-21 in glioblastoma-derived cell lines results in increased expression of its target, programmed cell death 4 (Pdcd4), a known tumor-suppressor gene. In addition, our data indicate that either downregulation of mir-21 or overexpression of its target, Pdcd4, in glioblastoma-derived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar. Using a glioblastoma xenograft model in immune-deficient nude mice, we observe that glioblastoma-derived cell lines in which mir-21 levels are downregulated or Pdcd4 is over-expressed exhibit decreased tumor formation and growth. Significantly, tumors grow when the glioblastoma-derived cell lines are transfected with anti-mir-21 and siRNA to Pdcd4, confirming that the tumor growth is specifically regulated by Pdcd4. These critical in vivo findings demonstrate an important functional linkage between mir-21 and Pdcd4 and further elucidate the molecular mechanisms by which the known high level of mir-21 expression in glioblastoma can attribute to tumorigenesis--namely, inhibition of Pdcd4 and its tumor-suppressive functions.
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TL;DR
In glioblastoma-derived cell lines and primary tumors, high miR-21 is inversely associated with the tumor suppressor Pdcd4; inhibiting miR-21 or overexpressing Pdcd4 reduces proliferation, increases apoptosis, and suppresses anchorage-independent growth. In nude-mouse xenografts, anti-miR-21 or Pdcd4 overexpression reduces tumor growth, and siRNA against Pdcd4 reverses the anti-miR-21 effect, supporting Pdcd4 as a key mediator.
Key findings
- miR-21 was elevated in all 7 glioblastoma-derived cell lines and all 13 glioblastoma tumors examined, while Pdcd4 protein was undetectable in primary glioblastoma tissues and cell lines compared with normal brain. Anti-miR-21 transfection increased Pdcd4 protein at 24, 48, and 72 hours.
- Anti-miR-21 treatment decreased proliferation, increased TUNEL-positive apoptosis, increased G0/G1 and decreased S-phase fraction, and reduced soft-agar colony formation by 65% (10 mM anti-miR-21) and 75% (30 mM anti-miR-21) in 3 independent experiments; U251 and U87 cells treated with anti-miR-21 formed 70% and 60% fewer colonies, respectively.
- Pdcd4 overexpression increased apoptosis and decreased colony formation. Anti-miR-21 plus Pdcd4 siRNA restored colony numbers similar to untreated controls; cells treated with anti-miR-21 and Pdcd4 siRNA produced 85% of the colonies seen with anti-miR-21 alone.
- In xenografts, anti-miR-21 reduced tumor growth by 30% at day 30 (P = .01); Pdcd4 overexpression produced a 90% decrease (P = .001) or complete lack of tumor growth. In 5 independent xenograft experiments, only 5 of 24 U251 GFP+Pdcd4 and 6 of 24 U87 GFP+Pdcd4 mice developed detectable tumors by day 30, and these were on average 90% smaller. Anti-miR-21 plus Pdcd4 siRNA tumors grew comparably to controls, reaching 1.5 cm³ by day 30. Pdcd4 was undetectable in 4 individual tumors arising from Pdcd4-overexpressing lines.
Methods
- Glioblastoma-derived cell lines SNB19, U251, U87, and SF767 were used with primary glioblastoma and normal brain samples. Stable Pdcd4-expressing polyclonal and monoclonal cultures were derived; transient transfections used anti-miR-21, negative/toxicity control, and Pdcd4 siRNA. Assays included Northern blot, Western blot, stem-loop real-time PCR, proliferation counts, TUNEL apoptosis, cell-cycle flow cytometry, and soft-agar colony formation.
- Xenografts used female 4–6-week-old Nude-Foxn1 nu mice injected subcutaneously in the flank with 5 × 10⁶ cells. Tumor size was measured in 3 dimensions, volume calculated as ellipsoid, and tumors imaged with the IVIS 200 Xenogen system. Data were from 5 independent xenograft experiments (total n = 24 animals per condition); statistics used unpaired two-tailed Student t test with P < .05, and experiments were performed at least 3 times.
Limitations
- Stated: xenografts were not of sufficient size to analyze DNA, RNA, and protein, so only Pdcd4 protein was measured. The authors note that rare cells may escape Pdcd4 inhibition through altered transgene integration or epigenetic inactivation, and small tumors from anti-miR-21-treated cells may arise from untransfected cells. They also note miR-21 can target several genes; anti-miR-21 plus Pdcd4 siRNA still produced 85% of colonies compared with anti-miR-21 alone, suggesting additional miR-21 targets.
- Evident: the in vivo work uses subcutaneous xenografts in immune-deficient nude mice rather than orthotopic or patient-derived models, and no survival or clinical outcome data are reported. Transfection efficiency was 80%–90%, leaving potential untransfected cells in treated populations.
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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
“Also, TUNEL staining revealed enhanced apoptosis in U251 (Fig. 3B) and U87 cells (data not shown) treated with anti-mir-21, compared with cells cultured in either medium alone or with NS control.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth
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
“Western blot analyses of nuclear proteins isolated from these same U251 and U87 cultures exhibited increased Pdcd4 protein levels 24, 48, and 72 h after anti-mir-21 treatment (Fig. 2B, lanes 3 -5 and 8-10, respectively).”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Down Regulation of mir-21 Expression in Glioblastoma-Derived Cell Lines Results in Enhanced Pdcd4 Expression
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 apoptosis in U87 cells treated with anti-mir-21 or stably over expressing Pdcd4 (U87 Pdcd4 ) was also observed (data not shown).”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth
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 U251 Pdcd4 polyclonal cell culture showed a decrease in colony number compared to cells that did not have elevated Pdcd-4 levels.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth
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
“In addition, our data indicate that either downregulation of mir-21 or overexpression of its target, Pdcd4, in glioblastomaderived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar.”
- Also stated in: § Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth · plain
“Also, TUNEL staining revealed enhanced apoptosis in U251 (Fig. 3B) and U87 cells (data not shown) treated with anti-mir-21, compared with cells cultured in either medium alone or with NS control.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth · plain
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 demonstrate that downregulation of mir-21 in glioblastoma-derived cell lines results in increased expression of its target, programmed cell death 4 (Pdcd4), a known tumor-suppressor gene.”
- Also stated in: § Down Regulation of mir-21 Expression in Glioblastoma-Derived Cell Lines Results in Enhanced Pdcd4 Expression · plain
“Western blot analyses of nuclear proteins isolated from these same U251 and U87 cultures exhibited increased Pdcd4 protein levels 24, 48, and 72 h after anti-mir-21 treatment (Fig. 2B, lanes 3 -5 and 8-10, respectively).”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Down Regulation of mir-21 Expression in Glioblastoma-Derived Cell Lines Results in Enhanced Pdcd4 Expression · plain
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 addition, our data indicate that either downregulation of mir-21 or overexpression of its target, Pdcd4, in glioblastomaderived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar.”
- Also stated in: § Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth · plain
“We observed decreased cell numbers in cultures treated with anti-mir-21, compared with cultures that were incubated in regular media or transfected with a nonspecific negative toxicity control (Fig. 3A).”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth · plain
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 addition, our data indicate that either downregulation of mir-21 or overexpression of its target, Pdcd4, in glioblastomaderived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar.”
- Also stated in: § Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth · plain
“The U251 Pdcd4 polyclonal cell culture showed a decrease in colony number compared to cells that did not have elevated Pdcd-4 levels.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth · plain
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 addition, our data indicate that either downregulation of mir-21 or overexpression of its target, Pdcd4, in glioblastomaderived cell lines leads to decreased proliferation, increased apoptosis, and decreased colony formation in soft agar.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > 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
“Clonal isolates and a polyclonal culture of U251 overexpressing Pdcd-4, U251 Pdcd4 demonstrated increased spontaneous apoptosis, as determined by TUNEL staining, compared with the parental cells from which they were derived (Fig. 3B and C).”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 15
- Probably not a substantial claim. 19
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 also observed decreased numbers of colonies formed by U87 cells that were treated with anti-mir-21 or stably over-expressed Pdcd4 (U87 Pdcd4 ) (Fig. 4B).”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth
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
“Subcutaneous injection of 5 × 10 6 cells from U251 GFP or U87 GFP in the flank of immunosuppressed mice gave rise to tumors that were first palpable by day 7 after injection and that developed to 1.5 cm 3 in size by day 30.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Downregulation of mir-21 or Overexpression of Pdcd4 Results in Reduction of Glioblastoma Xenograft Growth that is Reversed by siRNA to Pdcd4
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
“High cellularity and microvascular prolifer- ation (Supplemental Fig. S1) and the presence of necrosis (Supplemental Fig. S2), all of which are defining features of glioblastoma, are evident in these tumors.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Downregulation of mir-21 or Overexpression of Pdcd4 Results in Reduction of Glioblastoma Xenograft Growth that is Reversed by siRNA to Pdcd4
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.
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 these in vivo experiments mice that received cell lines overexpressing Pdcd4 showed a substantial decrease in tumor size and/or complete ablation of tumor growth (Fig. 5A).”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“In addition to being a pro-apoptotic gene, Pdcd4 is a suppressor of malignant transformation and tumor progression and has been shown to inhibit invasion and intravasation by tumor cells.16,22 -25”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Downregulation of mir-21 or Overexpression of Pdcd4 Results in Reduction of Glioblastoma Xenograft Growth that is Reversed by siRNA to Pdcd4
What the sources say
- Not matchedcites [16]
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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
“We routinely achieved 80% -90% transfection efficiency.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Down Regulation of mir-21 Expression in Glioblastoma-Derived Cell Lines Results in Enhanced Pdcd4 Expression
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.
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In the paper
“MiR-21 has been identified as one of the most commonly overexpressed miRNAs in solid tumors.9,10”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > M
What the sources say
- Not matchedcites [9]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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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.
- Not matched
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In the paper
“Glioblastomas are the most malignant brain tumors of glial origin.21,28”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [21]
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In the paper
“Previous work in our laboratory 8 and by others 9 -14 has demonstrated that miR-21 is a member of a class of miRNAs that are frequently overexpressed in solid tumors and may contribute to oncogenesis.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [8]
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Strength:hedged· not yet calibratedCausal:conditional· 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.
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In the paper
“Low levels of mir-21 are expressed in grade II and grade III gliomas, whereas higher levels are observed in glioblastoma.13,15”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > M
What the sources say
- Not matchedcites [13]
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Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Not matched
In the paper
“because mir-21 can potentially target several genes, 11”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Inhibiting mir-21 expression in glioblastoma-derived cell lines results in decreased proliferation, increased apoptosis, and diminished anchorage-independent growth
What the sources say
- Not matchedcites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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In the paper
“All of the experiments were performed at least 3 times.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Statistical Analysis
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.
In the paper
“They are also among the most resistant of all human tumors to available modalities of treatment, perhaps because of their genetic heterogeneity and invasiveness.28”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [28]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:hedged· not yet calibratedCausal:conditional· 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
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In the paper
“In glioblastoma, mir-21 is overexpressed, and its expression correlates with glioma grade.8,10 -15”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > M
What the sources say
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Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Not matched
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
“Mice that received U251 GFP or U87 GFP lines after transfection with anti-mir-21 and siRNA to PDCD4 significantly gave rise to tumors that were comparable to the untreated controls (Fig. 5A and 5C), confirming that the tumor growth is specifically regulated by PDCD4 and represents a crucial functional linkage between mir-21 and PDCD4 in vivo.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
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None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“Negative regulation of Pdcd4 by mir-21 has recently been demonstrated in glioblastoma and in several other tumors.41 -44”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [41]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
- Not matched
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In the paper
“Pdcd4, a described target of mir-21, 16 -18 has been characterized as both a tumor suppressor 16,21 -25 and a pro-apoptotic gene that may function by binding eukaryotic initiation factor 4A (eIF4A) and inhibiting translation initiation.38 -40”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [38]
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- Not matchedcites [39]
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Strength:hedged· not yet calibratedCausal:conditional· 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
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In the paper
“Elevated expression of miR-21 has been documented in several different types of cancer including those arising in breast, 9,16 brain, 11 -15 prostate, 29 ovaries, 30,31 colon, 32 and pancreas, 33 as well as cervical carcinoma, 34 hepatocellular carcinoma, 35 chronic lymphocytic leukemia, 36 and acute myeloid leukemia.37”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [9]
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- Not matchedcites [29]
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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.
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In the paper
“Although an additional major pathway of Pdcd4 inactivation is the increased proteasomal degradation of Pdcd4 due to its phosphorylation by Akt and p70(S6K), 46 our findings provide strong evidence that, by inhibition of Pdcd4 by mir-21, over-expression contributes to glioblastoma growth.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [46]
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.
- Not matched
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In the paper
“This is similar to the antiapoptotic activity of mir-21 in hepatocellular carcinoma where mir-21 has been shown to downregulate PTEN, initiate caspase activity, and lead to decreased apoptosis.35,45”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [35]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [45]
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
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
“However, our data suggest that, along with suppression of Pdcd4's pro-apoptotic function, downregulation of its tumor-suppressive activity also contributes to the oncogenic role of mir-21.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“The anti-apoptotic activity for mir-21 in glioblastoma lines that we observed is consistent with previously published data.11,12”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [11]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [12]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
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.
- Not matched
In the paper
“For example, miR-21 has been shown to inhibit apoptosis by regulating Bcl-2 in murine breast cancer model 49,50 and to inhibit gemcitabine-induced apoptosis by modulating PTEN and the PI3K pathway.51”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [51]
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.
- 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
“Data are representative of 5 independent xenograft experiments (total n ¼ 24 animals per condition).”
- Also stated in: § Discussion · plain
“Data are averages of 5 independent xenograft experiments (total n ¼ 24 animals per condition) + SEM.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
Strength:plain· not yet calibratedn = 24Tests✓ 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.
- Also stated in: § Discussion · plain
In the paper
“Consistent with this idea is the observation that mir-21 regulation of 2 important matrix metalloproteinase inhibitors, RECK and TIMP3, may be of importance in vivo.13”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [13]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:hedged· not yet calibratedCausal:conditional· 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.
- Not matched
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 finding that high levels of Pdcd4 expression inhibited tumor growth suggests that inhibiting Pdcd4 degradation or enhancing its expression may be a therapeutic strategy of importance for glioblastoma.”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
None of the sources cited for this claim could be matched to a paper in Crossref, so there is nothing to check it against.
In the paper
“For example, miR-21 has been shown to inhibit apoptosis by regulating Bcl-2 in murine breast cancer model 49,50 and to inhibit gemcitabine-induced apoptosis by modulating PTEN and the PI3K pathway.51”
§ Downregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo > Discussion
What the sources say
- Not matchedcites [49]
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Not matchedcites [50]
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.
- Not matched
The paper relies on this without support.
The effect of mir-21 regulation of Pdcd4 on specific biological activities (apoptosis, proliferation, anchorage-independent growth, or in vivo growth of glioblastoma xenografts) has not been studied.
“However, the effect of mir-21 regulation of Pdcd4 on specific biological activities of pathologic potential (eg, apoptosis, proliferation, anchorage-independent growth, or more significantly, in vivo growth of glioblastoma xenografts) has, to our knowledge, not been studied.”
The paper relies on this without support.
Anchorage-independent growth in soft agar correlates closely with tumorigenicity of transformed cells.
“Anchorage-independent growth assayed in soft agar is a characteristic of transformed cells that correlates closely with their tumorigenicity.”
The paper relies on this without support.
The effect of mir-21/Pdcd4 regulation on specific biological activities, such as apoptosis, proliferation, or anchorage-independent growth, has not been studied.
“Although mir-21 has been shown to regulate Pdcd4 in glioblastoma, 18 the effect of mir-21/Pdcd4 regulation on specific biological activities, such as apoptosis, proliferation, or anchorageindependent growth, has not been studied.”
The paper relies on this without support.
The effect on in vivo growth of glioblastoma cells of mir-21/Pdcd4 has not been explored.
“More significantly, the effect on in vivo growth of glioblastoma cells of mir-21/Pdcd4 has not been explored.”
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 [18]
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
“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 [18]
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 [18]
The cited source says what the claim attributes to it.
In the citing paper
“Previously, we showed that overexpression of PDCD4 leads to decreased anchorage-independent growth in glioblastoma (GBM)-derived cell lines and decreased tumor growth in a GBM xenograft model.”
From Tumor suppressor PDCD4 inhibits NF-κB-dependent transcription in human glioblastoma cells by direct interaction with p65 (2014) · cites this paper as [13]
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.
Colony-count rescue is described in opposite directions
MinorThe results say that adding siRNA to Pdcd4 increases colony formation relative to anti-mir-21 alone. The discussion instead says the combined treatment produces 85% as many colonies as anti-mir-21 alone, which would be a decrease.
“Compared with cells that were treated with anti-mir-21 only, U251 or U87 that were treated with anti-mir-21 and siRNA to Pdcd4 produced higher number of colonies, similar to those formed by untreated U251 or U87 (Fig. 4A and B).”
“Interestingly, cells treated with anti-mir-21 and siRNA to Pdcd4 produced 85% of the colonies compared to cells treated with anti-mir-21 only.”
TUNEL results are assigned to the cell-cycle figure panel
MinorThe results cite Fig. 3B for TUNEL staining, but the figure caption identifies panel B as cell-cycle analysis; it identifies panel C as TUNEL staining.
“Also, TUNEL staining revealed enhanced apoptosis in U251 (Fig. 3B) and U87 cells (data not shown) treated with anti-mir-21, compared with cells cultured in either medium alone or with NS control.”
“(B) Cell-cycle analyses of U251 and U87 cells and cells transfected with non-specific negative/toxicity anti-mir (NS) control (30 mM) or anti-mir-21 (30 mM) as well as U251 Pdcd4 and U87 Pdcd4 cells.”
Figure 1B identifies different Western blot targets
MinorThe caption calls panel B a Western blot of mir-21, then says the blot quantifies Pdcd4 protein using an anti-Pdcd4 antibody.
“(B) Western blot analysis of mir-21 in primary tissues (2H, 4A10, 35A28, and 52A28) and GBM-derived cell lines (SNB19, U251, U87, and SF767), compared with normal human brain samples (NB4330 and NB4126).”
“Forty micrograms of protein from whole-cell lysates were loaded in each well for quantifying Pdcd4 protein levels by Western blot analysis using an anti-Pdcd4 antibody.”
Cited works that were retracted
Works this paper cites that were later retracted, from the retraction notices publishers deposit. Major when the notice came out before this paper was published.
Cites a retracted work: 10.1002/jcb.20982
InfoThe cited work was retracted on 2025-04-28 (notice 10.1002/jcb.70023), not before this paper was published (2011-06-01).
Cited work 10.1002/jcb.20982 · retracted 2025-04-28 · notice 10.1002/jcb.70023 · this paper published 2011-06-01
“Kutay, 2006, Journal of cellular biochemistry, 99, 671, 10.1002/jcb.20982”
Citations
Cites
1 retracted
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MicroRNA-21 Regulates Expression of the PTEN Tumor Suppressor Gene in Human Hepatocellular Cancer
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MicroRNA-21 Is an Antiapoptotic Factor in Human Glioblastoma Cells
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MicroRNA Signatures in Human Ovarian Cancer
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2 of the 55 references couldn’t be matched to a known paper.
Research works printed but not linked: 3
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A 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
The protean world of non-coding RNAs in glioblastoma
Paulmurugan, R., Malhotra, M., & Massoud, T. F. (2019) · Journal of Molecular Medicine · doi:10.1007/s00109-019-01798-6 · Cited by 25
Liao, Y.-C., Cheng, T., Tu, S., Chang, J., Guo, P., Chen, L.-C., & Ho, Y. (2023) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2023.07.013 · Cited by 26
Reducible 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
MicroRNA-21, induced by high glucose, modulates macrophage apoptosis via programmed cell death 4
Shang, Y., Fang, N., Wang, F., Wang, H., Wang, Z., Tang, M., Peng, J., Zhang, Y., Zhang, W., & ZHONG, M. (2012) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3398 · Cited by 25
Critical role of HOX transcript antisense intergenic RNA (HOTAIR) in gliomas
Angelopoulou, E., Paudel, Y. N., & Piperi, C. (2020) · Journal of Molecular Medicine · doi:10.1007/s00109-020-01984-x · Cited by 24
“Furthermore, PDCD4 downregulation by miR-21 could promote glioma cell proliferation in vivo [101].”
BackgroundGuha, A., Waris, S., Nabors, B., Filippova, N., Gorospe, M., Kwan, T., & King, P. H. (2021) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2021.114082 · Cited by 23
δ-Opioid Receptor Activation and MicroRNA Expression of the Rat Cortex in Hypoxia
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“Enhancement of miR-21 expression is associated with increased cell proliferation, PDCD4 and Sprouty repression, and chemotherapy resistance in models of cardiac hypoxia preconditioning, pulmonary artery smooth muscle cells, glioblastoma and ovarian tumors [32,33,34,35,36].”
MicroRNA-based therapy for glioblastoma: Opportunities and challenges
Lei, Q., Yang, Y.-M., Zhou, W., Liu, W., Li, Y., Qi, N., Li, Q., Wen, Z., Ding, L., Huang, X., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175388 · Cited by 24
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“Moreover, an increase in miR-21 expression has been observed in many cancers, which likely contributes to the frequently observed loss of PDCD4 [25-27].”
BackgroundMicroRNA-21 induces cisplatin resistance in head and neck squamous cell carcinoma
Sheng, S., Su, W., Mao, D., Li, C., Hu, X., Deng, W., Yao, Y., & Ji, Y. (2022) · PLoS ONE · doi:10.1371/journal.pone.0267017 · Cited by 25
“Studies of miR-21 upregulation and its tumour-promoting roles have been reported in various cancers, for example, in lung cancer [27], gastrointestinal cancer [28], colorectal cancer [29], breast cancer [30], glioblastoma [31], oral cancer, and HNSCC [32, 33].”
BackgroundMolecular mechanisms of microRNAs in glioblastoma pathogenesis
Behrooz, A. B., Latifi‐Navid, H., Nezhadi, A., Świat, M., Łoś, M., Jamalpoor, Z., & Ghavami, S. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2023.119482 · Cited by 22
Chen, Y., Bian, Y., Zhao, S., Kong, F., & Li, X. (2016) · Oncology Letters · doi:10.3892/ol.2016.5323 · Cited by 22
“Gaur et al (27) reported that PDCD4 downregulation by miRNA-21 promotes glioblastoma proliferation in vivo.”
Efficient NMR Screening Approach to Discover Small Molecule Fragments Binding Structured RNA
Shortridge, M. D., & Varani, G. (2021) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.1c00109 · Cited by 21
HypoxamiRs: the hidden architects of tissue adaptation in hypoxia
Egea, V. (2025) · Cell Death and Disease · doi:10.1038/s41419-025-08091-0 · Cited by 19
“Additionally, miR-21 downregulates programmed cell death 4 (PDCD4), reducing apoptosis and supporting endothelial cell viability in ischemic environments [59].”
Epigenetic Regulation by lncRNA GAS5/miRNA/mRNA Network in Human Diseases
Nguyen, L. N. T., Pyburn, J. S., Nguyen, N. T., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26031377 · Cited by 19
“Additionally, the miR-21-mediated suppression of apoptosis has been linked to the suppression of programmed cell death 4 (PDCD4), resulting in continuous cell cycle progression [38,39].”
Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells
Pin, G., Huanting, L., Chengzhan, Z., Xinjuan, K., Yugong, F., Wei, L., Shifang, L., Zhaojian, L., Kun, H., Weicheng, Y., et al. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.593685 · Cited by 18
“The analysis indicated PDCD4 to be significantly down-regulated in seven glioma cell lines than in normal astrocytes (Figures 1B,D), consistent with previous studies (Gaur et al., 2011; Liwak et al., 2013).”
ResultImpact of dietary compounds on cancer-related gut microbiota and microRNA
Rajoka, M. S. R., Jin, M., Zhao, H., Li, Q., Shao, D., Huang, Q., & Shi, J. (2018) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-018-8935-3 · Cited by 19
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The Role of Micro RNAs in Regulating PI3K/AKT Signaling Pathways in Glioblastoma
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“Additionally, miR-21 exerts its oncogenic effects targeting other downstream of mTORC1 as S6K and 4E-BP1(70, 71).”
BackgroundExploring the Role of microRNAs in Glioma Progression, Prognosis, and Therapeutic Strategies
Tluli, O., Al-Maadhadi, M., Al-Khulaifi, A. A., Akomolafe, A. F., Al-Kuwari, S. Y., Al-Khayarin, R. S., Maccalli, C., & Pedersen, S. (2023) · Cancers · doi:10.3390/cancers15174213 · Cited by 18
“Predictably, gliomas demonstrated increased sensitivity to chemotherapy upon the inhibition of miR-21 [12].”
BackgroundIntegration of MicroRNAs with nanomedicine: tumor targeting and therapeutic approaches
Telkoparan‐Akillilar, P., Chichiarelli, S., Tucci, P., & Saso, L. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1569101 · Cited by 19
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“In numerous tumors, PDCD4 has been shown to act as a tumor suppressor [64,65].”
BackgroundComparison of microRNA expression levels between initial and recurrent glioblastoma specimens
Ilhan‐Mutlu, A., Wöehrer, A., Berghoff, A. S., Widhalm, G., Marosi, C., Wagner, L., & Preusser, M. (2013) · Journal of Neuro-Oncology · doi:10.1007/s11060-013-1078-6 · Cited by 16
Cerebrospinal fluid biomarkers of malignancies located in the central nervous system
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Interplay Between Non-Coding RNAs and Programmed Cell Death Proteins
Ghafouri‐Fard, S., Hussen, B. M., Mohaqiq, M., Shoorei, H., Baniahmad, A., Taheri, M. N., & Jamali, E. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.808475 · Cited by 15
Overcoming resistance to rapalogs in gliomas by combinatory therapies
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Discovery of a novel role of tumor suppressor PDCD4 in stimulation of translation termination
Shuvalova, E., Egorova, T., Ivanov, A., Shuvalov, A. V., Biziaev, N., Mukba, S., Pustogarov, N., Terenin, I. M., & Alkalaeva, E. Z. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101269 · Cited by 15
“Accordingly, PDCD4 overexpression inhibits cancer cell proliferation and tumor growth (10).”
BackgroundGOLPH3 Regulates Exosome miRNA Secretion in Glioma Cells
Hu, P., Wang, K., Zhou, D., Wang, L., Zhao, M., Wang, W., Zhang, Y., Liu, Y., Yu, R., & Zhou, X. (2020) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01535-6 · Cited by 14
“It is reported that down-regulation of miR-21 reduces the oncogenic potential of GBM cell lines (Krichevsky and Gabriely 2009) and decreases tumor growth in nude mice (Gaur et al. 2011; Zhou et al. 2010).”
MicroRNA biosensors for detection of glioblastoma
Fattahi, M., Maghsudlu, M., Razipour, M., Movahedpour, A., Ghadami, M., Alizadeh, M., Khatami, S. H., Taheri‐Anganeh, M., Ghasemi, H., Ghasemi, H., et al. (2024) · Clinica Chimica Acta · doi:10.1016/j.cca.2024.117829 · Cited by 13
Synergistic regulatory effects of microRNAs on brain glioma cells
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“…the miR‑17‑92 cluster, miR‑26a and miR‑221/222, are upregulated in glioma and promote the proliferation, migration and invasion of cancer cells (10-13), whereas 33 miRNAs, including miR-7, miR-137, miR-145, the miR-181 family and miR‑195, are downregulated and inhibit apoptosis in cancer cells…”
MicroRNA therapeutics in glioblastoma: Candidates and targeting strategies
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MicroRNA Therapeutics in Triple Negative Breast Cancer
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“, reported that miR-29 mediated EMT (epithelial mesenchymal transition) and induced metastasis in breast cancer [58,59] miR-21 is an important regulator of development and progression in case of TNBC and miR-21 is highly upregulated in the solid tumor cells of breast cancer [60,61].”
BackgroundHu, J., Wang, Z., Jinjun, W., Jian, Y., Dai, J., Wang, X., & Xiong, W. (2020) · OncoTargets and Therapy · doi:10.2147/ott.s258251 · Cited by 11
“MiR-21 has been found to negatively regulate PDCD4 expression in breast cancer,(26) colorectal cancer,(27) malignant glioblastoma tumors.(28) HBx repressed PDCD4 expression via the induction of miR-21 in HCC.”
BackgroundDeletion of miR-15a inhibited glioma development via targeting Smad7 and inhibiting EMT pathway
Guo, Y., Gao, X., An, S., et al. (2021) · Aging · doi:10.18632/aging.203684 · Cited by 10
“In gliomas, miR-21 can inhibit the expression of PDCD4, thus inhibit the apoptosis of glioma cells and promote cell proliferation and invasion [13].”
BackgroundThe Roles of MicroRNAs in Glioblastoma Biology and Biomarker
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“Antiapoptosis miR-21 PDCD4, HNRPK, TP53BP2, p63 up antiapoptosis Corsten (95), Gaur (96)”
BackgroundInfluentialLiu, Z., Su, D., Qi, X., & Ma, J. (2018) · Molecular Medicine Reports · doi:10.3892/mmr.2018.9259 · Cited by 10
“The protocol was described previously (22).”
Mo, Y., Adu‐Amankwaah, J., Qin, W., Gao, T., Hou, X., Fan, M., Liao, X., Jia, L., Zhao, J., Yuan, J., et al. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2279748 · Cited by 7
Microarray analysis of the aberrant microRNA expression pattern in gliomas of different grades
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Micro RNAs as a Diagnostic Marker between Glioma and Primary CNS Lymphoma: A Systematic Review
Ohadi, M. A. D., Aleyasin, M. S., Samiee, R., Bordbar, S., Maroufi, S. F., Bayan, N., Hanaei, S., & Smith, T. R. (2023) · Cancers · doi:10.3390/cancers15143628 · Cited by 6
“Other apoptotic targets of miR-21 include the phosphate and tensin homologous (PTEN) protein [33,34,38–40], programmed cell death gene 4 (PDCD4) [32,38,41], and tropomyosin 1 [36,42].”
BackgroundYang, Y., Chen, X., Han, H., Sun, J., Chen, S., Yang, C., Ma, Q., & Yang, J. (2021) · Scientific Reports · doi:10.1038/s41598-021-98913-w · Cited by 6
Inhibition of miR-21 Promotes Cellular Senescence in NT2-Derived Astrocytes
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Defining the regulatory role of programmed cell death 4 in laryngeal squamous cell carcinoma
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“Programmed cell death 4 (PDCD4), is a highly conserved protein that is widely expressed in normal and cancerous human tissues(Afonja et al. 2004; Asangani et al. 2008;Hiyoshi et al. 2009;Gaur et al. 2011).”
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“Many cancer studies have shown that PDCD4 is a gene known to be associated with promoting apoptosis 33–36 .”
The Role of Non-coding RNAs in the Pathogenesis of Glial Tumors
Kovalenko, T. F., Larionova, T. D., Антипова, Н. В., Shakhparonov, M. I., & Pavlyukov, M. S. (2021) · Acta Naturae · doi:10.32607/actanaturae.11270 · Cited by 5
Transitional Insight into the RNA-Based Oligonucleotides in Cancer Treatment
Tabasi, H., Mollazadeh, S., Fazeli, E., Abnus, K., Taghdisi, S. M., Ramezani, M., & Alibolandi, M. (2023) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-023-04597-5 · Cited by 5
“Therefore, this miRNA could be proposed as a target of interest to downregulate both PDCD4 and SERPINB5 , leading to the inhibition of cell growth and proliferation [84].”
Zai, H., Wu, X., Zhou, Y.-F., et al. (2024) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-024-05008-z · Cited by 5
“This down-regulation of PDCD4 by miR-21 has also been linked to the increased proliferation of glioblastoma in vivo [19].”
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Expression of microRNAs in tumors of the central nervous system in pediatric patients in México
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Pathogenic and Therapeutic Role of Micrornas in Glioblastoma Multiforme
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The Role of MicroRNAs in Chemoresistance
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“The expression of PDCD4 is regulated post-transcriptionally by microRNAs such as miR-21 [ 14 –16 ], and this process is intricately regulated by the RBPs HuR, TIA1 and La [ 17 –19 ] to maintain tight control of PDCD4 levels.”
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Programmed Cell Death Protein 4 -Expression in Urologic Tumors
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General Anesthesia and Perioperative Management via microRNA
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Ингибирование miR-21 способствует процессу старения полученных из клеток NT2 астроцитов
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Updates of Role of Stem Cells in Cancer Therapy
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“A study of engineered exosomes containing miRNA (especially miR-21) show they successfully downregulated target genes PDCD4 and RECK of the miR-21 in glioma cell lines [269].”
BackgroundDirectly Targeting RNA with Drug-like Small Molecules
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Drug Discovery for Chromatin Readers, Writers, Erasers, Remodelers and Epitranscriptomic Targets
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Practical and translational therapeutic elements for GBM therapy
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PDCD4: A Double-Edged Sword in Neurological Diseases
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Metadata
- Authors
- Gaur, A. B., Holbeck, S. L., Colburn, N. H., & Israel, M. A.
- Affiliations
- Dartmouth College (US)
- Corresponding author
- Gaur, A. B.
- Venue
- Neuro-Oncology
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-06-01
- Volume
- 13
- Issue
- 6
- Pages
- 580-590
- ISSN
- 1522-8517 (ISSN-L)
- 1523-5866
- PMC
- PMC3107097
- OpenAlex
- W2097617161
- Semantic Scholar
- baf2769011f484edff3d111bdecfc52cb2d992b6
- Cited by
- 180
- References
- 55
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 9 · 2022: 11 · 2021: 16 · 2020: 14 · 2019: 9 · 2018: 7 · 2017: 13 · 2016: 13 · 2015: 14 · 2014: 15 · 2013: 19 · 2012: 15
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuro-Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Funders
- U.S. Department of Health and Human Services
- National Institutes of Health
- National Cancer Institute
- 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 › Glioma Diagnosis and Treatment
- Keywords
- miR-21, PDCD4, glioblastoma, microRNA, tumor suppressor, cell proliferation, apoptosis, colony formation, xenograft tumor growth, carcinogenesis, post-transcriptional regulation
- MeSH terms
- Animals, Brain, Brain Neoplasms, Cell Adhesion, Cell Movement, Female, Glioblastoma, Humans, Mice, Nude, RNA, Messenger, Blotting, Northern, Blotting, Western, RNA-Binding Proteins, Apoptosis, Reverse Transcriptase Polymerase Chain Reaction, MicroRNAs, Cell Proliferation, Apoptosis Regulatory Proteins, Mice
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