Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells
Open accessAbstract
The programmed cell death 4 (PDCD4) tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing PDCD4 were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials.
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Written from the paper’s full text.
TL;DR
PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor; AKT2, but not AKT1 or AKT3, interacts with and suppresses PDCD4. PDCD4 overexpression reduces NF-κB activity and pro-angiogenic/pro-inflammatory mediators, blocks tumorigenesis, and prolongs survival in a mouse xenograft model.
Key findings
PDCD4 mRNA was significantly down-regulated in glioma among 16 TCGA cancer types and in seven glioma cell lines versus normal astrocytes. AKT2 mRNA was inversely associated with PDCD4 in TCGA clinical glioma samples (Spearman = −0.47, P = 0.002967), and AKT2 knockdown—but not AKT1 or AKT3 knockdown—increased PDCD4 expression. PDCD4 overexpression reduced nuclear p65 and p50, reduced NF-κB transcriptional activity, and lowered IL-5, CCL5, VEGF, and CXCL10 levels while enhancing CXCL5 and MIP3. Depletion of PDCD4 increased tube-like structure formation in HUVECs via VEGF-STAT3, and blocking VEGF or STAT3 with bevacizumab or cryptotanshinone suppressed this effect; PDCD4 overexpression suppressed tumorigenesis and prolonged survival in BALB/c nude mice, with fewer Ki67+ tumor cells.
Methods
The study used TCGA data analysis, human glioma cell lines and normal astrocytes, lentiviral shRNA knockdown and PDCD4 overexpression, immunoblotting, qRT-PCR, immunofluorescence, cytokine array, NF-κB luciferase reporter assay, colony formation, proximal ligation assay, HUVEC tube formation assays, and subcutaneous xenografts in 8-week-old BALB/c nude mice using 2 × 10^6 cells. Statistical analysis used mean ± SEM, unpaired Student’s t-test, and P < 0.05 as significant.
Limitations
The paper does not state a limitations section. Evident from the text: TCGA findings are correlative, most mechanistic evidence comes from cell lines and HUVEC assays, and in vivo work uses subcutaneous xenografts in immunocompromised mice rather than orthotopic glioma models. The cytokine array methods describe media from cancer fibroblasts with IRAK4 knockdown or scrambled vector, while the results describe PDCD4-overexpressing glioma cells, an apparent methods/results mismatch; the Results also state that PDCD4 knockdown suppressed colony formation and anchorage-independent growth, which conflicts with the title/abstract claim that down-regulation promotes proliferation.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
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Cites
Statistics
Claims the paper makes
- Findingown data
Over-expression of PDCD4 markedly reduces NF-κB transcriptional activity in U251 and A172 cells.
“luciferase reporter assay showed that the over-expression of PDCD4 markedly reduced the transcriptional activity of NF-κB in the U251 and A172 cells (Figure 3B).”
Quote in the paperSubstantial claim - Findingown data
Knockdown of PDCD4 increases formation of tube-like structures in HUVECs.
“knockdown of PDCD4 resulted in thicker walls of cells and more tubes, (Figures 4D,E) indicating increased formation of tube-like structures.”
Quote in the paperSubstantial claim - Findingown data
Over-expression of PDCD4 significantly suppresses tumorigenic potential of glioma cells in xenograft BALB/c nude mice.
“the over-expression of PDCD4 significantly suppressed the tumorigenic potential of glioma cells and prolonged the survival of tumor-bearing mice (Figures 5A,B).”
Quote in the paperSubstantial claim - Findingown data
Blocking VEGF or STAT3 in PDCD4-depleted cells completely suppresses formation of tube-like structures in HUVECs.
“blocking the activity of VEGF or STAT3 with bevacizumab or cryptotanshinone, respectively, in PDCD4-depleted cells completely suppressed the formation of tube-like structures in HUVECs (Figures 4D,E).”
Quote in the paperSubstantial claim - Findingown data
Over-expression of PDCD4 prolongs survival of tumor-bearing mice.
“the over-expression of PDCD4 significantly suppressed the tumorigenic potential of glioma cells and prolonged the survival of tumor-bearing mice (Figures 5A,B).”
Quote in the paperSubstantial claim
- Findingown data
PDCD4-over-expressing tumors have fewer proliferative cells (Ki67+ cells).
“immunofluorescence staining showed that PDCD4-over-expressing tumors had less proliferative cells (Ki67 + cells) (Figures 5C,D).”
Quote in the paperSubstantial claim - Findingown data
PDCD4 mRNA and protein levels are significantly down-regulated in seven glioma cell lines compared with normal astrocytes.
“The analysis indicated PDCD4 to be significantly down-regulated in seven glioma cell lines than in normal astrocytes (Figures 1B,D)”
Quote in the paperSubstantial claim - Findingown data
Over-expression of PDCD4 inhibits VEGF expression in U251 and A172 cell lines.
“we confirmed that over-expression of PDCD4 inhibited the expression of VEGF using western blot analysis in the U251 and A172 cell lines (Figure 4A).”
Quote in the paperSubstantial claim - Findingown data
Over-expression of PDCD4 significantly reduces nuclear levels of p65 and p50 proteins, but not RelB and c-Rel, in glioma cells.
“over-expression of PDCD4 significantly reduced the levels of p65 and p50 proteins, but no significant change in that of RelB and c-Rel (Figure 3A).”
Quote in the paperSubstantial claim - Findingown data
PDCD4 mRNA is significantly down-regulated in glioma among 16 cancer types analyzed from the TCGA database.
“Among the 16 cancer types (originating in the glial cells, thyroid, lung, liver, pancreas, head and neck, stomach, colon and rectum, urethra, bladder, ureters and renal pelvis, prostate, cervix, endometrium, and skin), PDCD4 was significantly down-regulated in glioma (Figure 1A).”
Quote in the paperSubstantial claim - Findingown data
Knockdown of AKT2, but not AKT1 or AKT3, increases PDCD4 expression in glioma cells.
“knockdown of AKT2, but not the AKT1 or AKT3 isoforms, resulted in increased expression of PDCD4 (Figure 2C).”
Quote in the paperSubstantial claim - Findingown data
AKT2 mRNA expression is inversely associated with PDCD4 mRNA in clinical glioma samples from TCGA (Spearman = -0.47, P = 0.002967).
“observed that the mRNA expression of AKT2, but not AKT1 or AKT3, was inversely associated with that of PDCD4 (Spearman = −0.47, P = 0.002967) (Figure 2A).”
Quote in the paperSubstantial claim - Findingown data
Inhibition of NF-kB activity rescues VEGF expression in cells with depleted levels of PDCD4.
“inhibition of NF-kB activity rescued the expression of VEGF in cells with depleted levels of PDCD4 (Figure 4B).”
Quote in the paperSubstantial claim - Interpretationown data
PDCD4 regulates the levels of IL-5, CCL-5, VEGF, and CXCL10.
“Taken together, our analysis indicates that PDCD4 regulates the levels of IL-5, CCL-5, VEGF, and CXCL10.”
Quote in the paperSubstantial claim - Interpretationown data
Induction of VEGF after knockdown of PDCD4 is dependent on the NF-kB pathway.
“This confirmed that induction of VEGF after knockdown of PDCD4 is dependent on the NF-kB pathway.”
Quote in the paperSubstantial claim - Interpretationown data
Depletion of PDCD4 promotes angiogenic activity via the VEGF-STAT3 pathway.
“Taken together, these data indicate that depletion of PDCD4 promotes angiogenic activity via the VEGF-STAT3 pathway.”
- Also stated in: § Abstract · plain
“depletion of levels of PDCD4 promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Interpretationown data
PDCD4 acts as a tumor suppressor in glioma cells.
“Taken together, our data suggests PDCD4 to be down-regulated in glioma cells and acts as a tumor suppressor.”
- Also stated in: § Abstract · plain
“In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Interpretationown data
PDCD4 regulates tumor angiogenesis.
“Taken together, our data supports the role of PDCD4 in regulation of tumor angiogenesis.”
Quote in the paperSubstantial claim
- May combine two claims. 9
- Classified as probably not a substantial claim. 6
- The quote only partly states this claim. 1
May combine two claims.
Findingown dataOver-expression of PDCD4 reduces levels of IL-5, CCL5, VEGF, and CXCL10 and enhances levels of CXCL5 and MIP3 in conditional medium from glioma cells.
“The data suggested that the levels of IL-5, CCL5, VEGF, and CXCL10 were reduced in the conditional medium from cells over-expressing PDCD4; however, the abundance of CXCL5 and MIP3 was enhanced by over-expression of PDCD4 (Figure 3C).”
- Also stated in: § PDCD4 Regulates Expression of IL-5, CCL-5, VEGF, and CXCL10 · boosted
“these changes were confirmed using real-time PCR analysis in U251 and A172 cells stably over-expressing PDCD4 (Figure 3D).”
Quote in the paperSubstantial claim- Also stated in: § PDCD4 Regulates Expression of IL-5, CCL-5, VEGF, and CXCL10 · boosted
May combine two claims.
Findingown dataAKT2, but not AKT1 or AKT3, interacts with PDCD4 in glioma cells.
“we performed the proximity ligation assay (PLA), which validated the formation of AKT2/PDCD4 complex in glioma cells”
- Also stated in: § Abstract · plain
“we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4”
Quote in the paperSubstantial claim- Also stated in: § Abstract · plain
May combine two claims.
Findingown dataKnockdown of PDCD4 in glioma cells enhances p-STAT3 levels, but not p-ERK or p-FAK1.
“knockdown of PDCD4 in glioma cells enhanced p-STAT3 levels, but not p-ERK or p-FAK1 (Figure 4C).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataKnockdown of PDCD4 suppresses colony formation in monolayer culture and anchorage-independent growth in soft agar in glioma cells.
“We found that the knockdown of PDCD4 suppressed colony formation in the monolayer culture, and anchorage-independent growth in soft agar assay (Figures 1E,F).”
- Also stated in: § Discussion · plain
“Depletion of PDCD4 suppressed colony formation and anchorage-independent growth in vitro.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · plain
May combine two claims.
Interpretationown dataTargeting PDCD4 by over-expression can block tumorigenesis and prolong overall survival duration.
“our data suggested that targeting PDCD4 by over-expression can block tumorigenesis and prolong overall survival duration”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe animal study was reviewed and approved by the Ethics Committee and Clinical Research Board at the Affiliated Hospital of Qingdao University.
“The animal study was reviewed and approved by the Ethics Committee and Clinical Research Board at the Affiliated Hospital of Qingdao University.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenAll human cell lines used were obtained from ATCC, which performs authentication on its own cell lines.
“All human cell lines were obtained from the American Type Culture Collection (ATCC), which performs authentication on its own cell lines.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe laboratory and clinical protocols of this study were approved by the Ethics Committee and Clinical Research Board at the Affiliated Hospital of Qingdao University (#170540091).
“The laboratory and clinical protocols of this study were approved by the Ethics Committee and Clinical Research Board at the Affiliated Hospital of Qingdao University (#170540091), Shangdong Province, China.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown dataAKT2, but not AKT1 or AKT3, interacts with and suppresses PDCD4 in glioma cells.
“Taken together, these data suggest that AKT2, but not AKT1 or AKT3, interacts with and suppresses PDCD4 in the glioma cells.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataEnhancing expression of PDCD4 can block tumorigenesis and prolong overall survival.
“our in vivo data suggested that enhancing expression of PDCD4 can block tumorigenesis and prolong overall survival”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims. The quote only partly states this claim.
Study design and conductnone givenAll experiments were performed three times in triplicates, and data are represented as mean ± SEM.
“All experiments were performed three times in triplicates, and data are represented as mean ± SEM.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll amplification reactions were performed in triplicates.
“All amplification reactions were performed in triplicates.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe specificity of the PCR products was confirmed by analyzing the melting curve.
“The specificity of the PCR products was confirmed by analyzing the melting curve.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The mechanism by which PDCD4 is down-regulated and regulates tumor growth in glioma remains elusive.
“However, the mechanism by which PDCD4 is down-regulated and regulates tumor growth remains elusive.”
“However, the functions of PDCD4 and the mechanism by which PDCD4 is down-regulated in human glioma cells remains to be completely elucidated.”
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?
PDCD4 inhibits cell proliferation by targeting AKT.
“Previous studies show that PDCD4 inhibits cell proliferation by targeting AKT (30).”
From Functional interaction between miR-505-3p and miR-21 contributes to GBM suppression (2026) · cites this paper as [30]
The Introduction and the in-vivo Results describe PDCD4 as suppressing growth in glioma. But the Results section on AKT2 reports that AKT2 interacts with and suppresses PDCD4, not that PDCD4 inhibits proliferation by targeting AKT. The proposed AKT mechanism is therefore not supported as stated. (LLM, conf=0.84)
Experimental — accuracy not yet measured
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.
Cytokine-array methods describe different cells and knockdown
MinorThe method specifies cancer fibroblasts with IRAK4 knockdown, whereas the reported cytokine-array result uses cells over-expressing PDCD4. These are different experimental conditions for the same assay.
“Serum-free DMEM was collected from 90% confluent cancer fibroblasts with stable knockdown of IRAK4 or scrambled vector”
“we collected the conditional medium from control cells or those over-expressing PDCD4 for the cytokine assay.”
PDCD4 knockdown is said to suppress growth despite the opposite conclusion
MinorThe results say PDCD4 knockdown suppressed colony formation and anchorage-independent growth. That conflicts with the paper's conclusion that down-regulation promotes proliferation.
“We found that the knockdown of PDCD4 suppressed colony formation in the monolayer culture, and anchorage-independent growth in soft agar assay (Figures 1E,F).”
“Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells”
Xenograft injection sites differ between methods and results
MinorThe methods place the subcutaneous injections in the mice's flanks, while the results place them in the bilateral armpits.
“subcutaneously injected into the flanks of immunocompromised 8-week-old BALB/c nude mice.”
“Parent U251 cells or U251 cells over-expressing PDCD4 were subcutaneously injected into the bilateral armpits of the nude mice.”
Cited K-Ras study does not match the described cancer or target
MinorThe text describes a PDCD4-targeting lung-cancer study, but the cited reference's title describes STAT1 and KRAS colon tumor growth.
“Furthermore, gene therapy by targeting PDCD4 in an activated K-Ras model was shown to block the development of lung cancer (Wang et al., 2016).”
“Wang S. Darini C. Desaubry L. Koromilas A. E. (2016). STAT1 promotes KRAS colon tumor growth and susceptibility to pharmacological inhibition of translation initiation factor eIF4A.”
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MethodDownregulation of Pdcd4 by mir-21 facilitates glioblastoma proliferation in vivo
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“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).”
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“To examine whether PDCD4 regulates VEGF in an NF-κB-dependent manner, we treated the PDCD4-depleted cells with IMD-0354 that selectively inhibits IKK activity in the NF-kB pathway (Tanaka et al., 2005).”
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“CCL-5, VEGF, and CXCL10 Previous studies showed that the expression of PDCD4 suppresses NF-kB transcriptional activation by inhibiting localization of p65 (Hwang et al., 2014; Su et al., 2017).”
BackgroundAKT Activation by Pdcd4 Knockdown Up-Regulates Cyclin D1 Expression and Promotes Cell Proliferation
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“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).”
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“CCL-5, VEGF, and CXCL10 Previous studies showed that the expression of PDCD4 suppresses NF-kB transcriptional activation by inhibiting localization of p65 (Hwang et al., 2014; Su et al., 2017).”
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PM2.5 induces pulmonary microvascular injury in COPD via METTL16-mediated m6A modification
Guo, X., Lin, Y., Lin, Y., Zhong, Y., Yu, H., Huang, Y., Yang, J., Cai, Y., Liu, F., Li, Y., et al. (2022) · Environmental Pollution · doi:10.1016/j.envpol.2022.119115 · Cited by 99 · see citing works
microRNAs (miRNAs) in Glioblastoma Multiforme (GBM)—Recent Literature Review
Makowska, M., Smolarz, B., & Romanowicz, H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043521 · Cited by 96 · see citing works
“In the T98G glioma cell line, the level of expression of the PDCD4 gene shows an inverse relationship with the expression of miR-21, and its reduction leads to the inhibition of the process of apoptosis, which is dependent on this gene [153,154].”
BackgroundLiu, T., Li, P., Li, J., Qi, Q., Sun, Z., Shi, S., Xie, Y., Liu, S., Wang, Y., Du, L., et al. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2021.09.003 · Cited by 59 · see citing works
Li, Y., Pang, J., Wang, J., Dai, G., Bo, Q., Wang, X., & Wang, W. (2023) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2023.102239 · Cited by 18 · see citing works
Remodeling the tumor immune microenvironment with oncolytic viruses expressing miRNAs
St-Cyr, G., Penarroya, D., Daniel, L., Giguère, H., Alkayyal, A. A., & Tai, L. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1071223 · Cited by 14 · see citing works
Liu, D., Ke, J., Liu, Y., Rao, H., Tang, Z., Liu, Y., Zhang, Z., You, L., Luo, X., Sun, Z.-Q., et al. (2021) · Molecular Carcinogenesis · doi:10.1002/mc.23345 · Cited by 12 · see citing works
“complex with AKT in regulating cancer cell proliferation, angiogenesis, and tumorigenesis.(24) Recently, another report demonstrated YB1 and AKT can form a complex to regulate gastric cancer cisplatin resistance.”
BackgroundLi, H., Ouyang, J., & Liu, R. (2023) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2023.175697 · Cited by 11 · see citing works
Ajayi, I. I., Fatoki, T. H., Alonge, S. A., Famusiwa, C. D., Saliu, I. O., Akinlolu, O. S., Onodugo, C. A., & Ojo, R. T. (2024) · Journal of Food Bioactives · doi:10.31665/jfb.2024.18374 · Cited by 6 · see citing works
“Depletion of PDCD4 levels promotes angiogenic activity of glioma cells through the VEGF-STAT3 pathway (Pin et al., 2020 ).”
BackgroundLi, S., Han, L.-F., He, Y., & Wang, X. (2022) · World Journal of Hepatology · doi:10.4254/wjh.v14.i12.1997 · Cited by 2 · see citing works
Tahoon, D. M., Khattab, H. A., Nasif, E., Elkholy, R. A., Elseady, W. S., Hamama, M., Saadawy, S. F., & Elkholy, R. A. (2023) · Bulletin of Pharmaceutical Sciences Assiut · doi:10.21608/bfsa.2023.301261 · Cited by 2 · see citing works
Vallés‐Martí, A., Böttger, F., Yau, E., Tejjani, K., Meijs, L. A. M., Sharma, S., Mumtaz, M., Large, T. Y. S. L., Erozenci, L. A., Dekker, D., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.12.19.572293 · Cited by 2 · see citing works
Poveda, M. C., Hardy, O. M., Laidlaw, R. F., Otto, T. D., & Maizels, R. M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.09.579622 · Cited by 2 · see citing works
“…a suite of histone genes ( Hist1h4h, Hist1h1c, Hist1h3c ) 64 , RNA processing and translation-related genes ( Eef1a1, Eef1b2, Pcbp2, Pdcd4, Rbm5, Sf3b1 ), and genes associated with protein quality control suggest reinvigorated metabolic activity 65-67 and recovery from stress 68, 69 (Fig.”
Carlos, F.-M. J., Gabriel, D. L. T.-C. C., Genoveva, P.-P. A., et al. (2022) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2022.104032 · Cited by 1 · see citing works
Chen, R., Wang, Z., Bing, W., Liu, D., & Xu, Y. (2025) · Molecular Biology Reports · doi:10.1007/s11033-025-11083-0 · Cited by 1 · see citing works
Vallés‐Martí, A., Böttger, F., Yau, E., Tejjani, K., Meijs, L. A. M., Sharma, S., Mumtaz, M., Large, T. Y. S. L., Erozenci, L. A., Dekker, D., et al. (2024) · eLife · doi:10.7554/elife.94988.1 · Cited by 1 · see citing works
Functional interaction between miR-505-3p and miR-21 contributes to GBM suppression
Banadkooki, M. Z., Soltani, B. M., & Mowla, S. J. (2026) · Scientific Reports · doi:10.1038/s41598-026-59926-5
“Previous studies show that PDCD4 inhibits cell proliferation by targeting AKT 30 .”
Vallés‐Martí, A., Böttger, F., Yau, E., Tejjani, K., Meijs, L. A. M., Sharma, S., Mumtaz, M., Large, T. Y. S. L., Erozenci, L. A., Dekker, D., et al. (2024) · eLife · doi:10.7554/elife.94988
PDCD4: A Double-Edged Sword in Neurological Diseases
Li, C., Zheng, K., Qiu, M. S., & Yang, J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05768-1
“This pathway is hyperactivated in gliomas due to loss of PTEN or gain-of-function mutations in PI3K, ensuring sustained PDCD4 downregulation [51].”
Yuan, Y., Zhu, B., Yang, L., Leng, Y., Chen, F., Yang, Z., Gu, W., & Zhang, K. (2026) · Biomedicines · doi:10.3390/biomedicines14050986
- Authors
- Pin, G., Huanting, L., Chengzhan, Z., Xinjuan, K., Yugong, F., Wei, L., Shifang, L., Zhaojian, L., Kun, H., Weicheng, Y., Yingying, L., Yongming, Q., & Yanan, Y.
- Affiliations
- Qingdao University (CN)
- Affiliated Hospital of Qingdao University (CN)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Yanan, Yu
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2020-11-12
- Volume
- 8
- Pages
- 593685-593685
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC7693433
- OpenAlex
- W3103931235
- Semantic Scholar
- bf88e06ddb5c99a712dbf6ca53864f761f54710f
- Cited by
- 18
- References
- 32
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 2
- FWCI
- 1.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cancer Mechanisms and Therapy
- Keywords
- PDCD4, glioma, tumor suppressor, AKT2, protein-protein interaction, angiogenesis, carcinogenesis, NF-κB signaling, vascular endothelial growth factor, STAT3, IL-5, RANTES, CXCL10, cell proliferation, apoptosis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-21.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-21.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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