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Cited by 66Glioma Diagnosis and TreatmentEpigenetics and DNA MethylationCancer-related molecular mechanisms research

PDCD4 gene silencing in gliomas is associated with 5′CpG island methylation and unfavourable prognosis

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Gao, Fei, Wang, Xiaoyan, Zhu, Faliang, Wang, Qun, Zhang, Xia, Guo, Chun, Zhou, Chengjun, Ma, Chunhong +4 more·2009·Journal of Cellular and Molecular Medicine
DOI 10.1111/j.1582-4934.2008.00497.xPMC PMC4496131
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Abstract

Programmed cell death 4 (PDCD4) is a newly described tumour suppressor that inhibits oncogenesis by suppressing gene transcription and translation. Loss of PDCD4 expression has been found in several types of human cancers including the most common cancer of the brain, the gliomas. However, the molecular mechanisms responsible for PDCD4 gene silencing in tumour cells remain unclear. Here we report the identification of 5′CpG island methylation as the predominant cause of PDCD4 mRNA silencing in gliomas. The methylation of the PDCD4 5′CpG island was found in 47% (14/30) of glioma tissues, which was significantly associated with the loss of PDCD4 mRNA expression (γ=−1.000, P < 0.0001). Blocking methylation in glioma cells using a DNA methyltransferase inhibitor, 5‐aza‐2′‐deoxycytidine, restored the PDCD4 gene expression, inhibited their proliferation and reduced their colony formation capacity. Longitudinal studies of a cohort of 84 patients with gliomas revealed that poor prognosis of patients with high‐grade tumours were significantly associated with loss of PDCD4 expression. Thus, our current study suggests, for the first time, that PDCD4 5′CpG island methylation blocks PDCD4 expression at mRNA levels in gliomas. These results also indicate that PDCD4 reactivation might be an effective new strategy for the treatment of gliomas.

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  • PDCD4 mRNA levels are decreased in many cancer tissues and cell lines as compared with corresponding normal tissues.

    “PDCD4 mRNA levels are decreased in many cancer tissues and cell lines as compared with the corresponding normal tissues [17,19,20].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [19]

    The Results (page not provided), particularly Table 2, show absent or reduced PDCD4 mRNA in many glioma samples and two glioma cell lines compared with non-tumour brain tissues. The Introduction reports PDCD4 loss or reduction in several other cancers, but does not establish that mRNA levels specifically are decreased across those cancer types. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • PDCD4 protein expression is often down-regulated in tumors but is maintained at high levels in a large number of tumors.

    “The expression of PDCD4-protein is often down-regulated in the tumors [17,18,19,20] but is maintained in high levels in a large number of tumors.”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [19]

  • Methylation of PDCD4 5′CpG islands is significantly correlated with loss of PDCD4 mRNA expression in 47% (14/30) of glioma tissues.

    “Gao et al. observed that the methylation of PDCD4 5′CpG islands was significantly correlated with the loss of PDCD4 mRNA expression in 47% (14/30) of glioma tissues [19].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [19]

  • Blocking methylation in glioma cells using the DNA methyltransferase inhibitor 5-aza-2 deoxycytidine restored PDCD4 expression and inhibited proliferation of the cells.

    “They demonstrated that blocking the methylation in glioma cells using the DNA methyltransferase inhibitor 5-aza-2 deoxycytidine restored PDCD4 expression and inhibited the proliferation of the cells [19].”

    From Control Mechanisms of the Tumor Suppressor PDCD4: Expression and Functions (2019) · cites this paper as [19]

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Research works printed but not linked: 32

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Authors
Gao, F., Wang, X., Zhu, F., Wang, Q., Zhang, X., Guo, C., Zhou, C., Ma, C., Sun, W., Zhang, Y., Chen, Y. H., & Zhang, L.
Affiliations
  • Shandong University (CN)
  • University of Pennsylvania (US)
Corresponding author
Zhang, Lining
ORCID
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2009-10
Volume
13
Issue
10
Pages
4257-4267
ISSN
  • 1582-1838 (ISSN-L)
  • 1582-4934
DOI
10.1111/j.1582-4934.2008.00497.x
PMC
PMC4496131
OpenAlex
W2094146259
Cited by
66
References
7
Citations by year
2026: 2 · 2024: 2 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 1 · 2016: 6 · 2015: 1 · 2014: 5 · 2013: 9 · 2012: 6
FWCI
1.69
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Cellular and Molecular Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (30628015, 30671976)
  • National Cancer Institute
Topics
  • Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
Keywords
PDCD4, glioma, DNA methylation, CpG island methylation, gene silencing, tumour suppressor, mRNA expression, hypomethylating agents, decitabine, cell proliferation, prognosis, tumor grade, epigenetic reactivation
MeSH terms
Adult, Base Sequence, Female, Glioma, Humans, Male, Middle Aged, Molecular Sequence Data, Prognosis, RNA, Messenger, Tumor Stem Cell Assay, Gene Expression Regulation, Neoplastic, Survival Analysis, RNA-Binding Proteins, Apoptosis, CpG Islands, DNA Methylation, Gene Silencing, Cell Line, Tumor, Cell Proliferation, Apoptosis Regulatory Proteins

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