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

Gao, Fei; Wang, Xiaoyan; Zhu, Faliang; Wang, Qun; Xia, Zhang; Guo, Chun; Zhou, Chengjun; Ma, Chao; Sun, Wei; Zhang, Yun; Chen, Youhai H.; Zhang, Lining

doi:10.1111/j.1582-4934.2008.00497.x

Cited by 63 publications

(69 citation statements)

References 38 publications

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“…It was reported that the PDCD4 protein and mRNA levels were often not correlated in human tumors (16,42). The loss of PDCD4 expression was associated with methylation of PDCD4 5'CpG islands in gliomas (42). In contrast, we have observed that the mRNA levels in hepatoma tissues were not suppressed compared with the levels in normal tissues (Ozaki et al unpublished data), despite suppression of the protein levels (13).…”

Section: Discussionmentioning

confidence: 50%

“…The degradation of the protein was stimulated through activation of the Akt-mTOR-S6K signaling pathway and the MAP kinase pathway (11,12,14). It was reported that the PDCD4 protein and mRNA levels were often not correlated in human tumors (16,42). The loss of PDCD4 expression was associated with methylation of PDCD4 5'CpG islands in gliomas (42).…”

Section: Discussionmentioning

confidence: 99%

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Expression patterns of the tumor suppressor PDCD4 and correlation with β-catenin expression in gastric cancers

Kakimoto

Shiraishi²,

Iwakiri³

et al. 2011

Oncol Rep

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Abstract. The expression patterns of PDCD4, a tumor suppressor, and β-catenin were immunohistologically investigated in gastric carcinoma tissues. In normal gastric tissues, PDCD4 was strongly expressed in the cell nuclei, but weakly expressed in the cytoplasm. In gastric adenocarcinoma tissues, nuclear PDCD4 expression was decreased, while cytoplasmic PDCD4 expression was unchanged or somewhat increased. In gastric signet ring cell carcinoma tissues, PDCD4 expression patterns were different from the expression patterns of the adenocarcinoma tissues, and PDCD4 was localized in the nuclei of the carcinoma cells as a belt in the middle of the epithelial layer. The nuclear localization of PDCD4 in the adenocarcinoma tissues was correlated with the membrane localization of β-catenin, the activation of which stimulates invasion of colon cancer cells. PDCD4 expression was correlated with β-catenin expression in gastric carcinoma cell lines, but not with E-cadherin, as the binding partner in the cell membrane.

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Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Expression patterns of the tumor suppressor PDCD4 and correlation with β-catenin expression in gastric cancers

Kakimoto

Shiraishi²,

Iwakiri³

et al. 2011

Oncol Rep

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“…Low PDCD4 expression levels correlate with poor outcomes in patients with glioblastoma multiforme (11). The frequent loss of PDCD4 in glioblastoma multiforme is partly due to epigenetic silencing secondary to 5' cytosine-phosphate-guanine island methylation (12), in addition to overexpression of microRNA (miRNA)-21, which targets PDCD4 mRNA for degradation (13). Although several studies have examined PDCD4 in glioma, the detailed molecular mechanisms underlying the role of PDCD4 in glioma remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Suppression of PDCD4 mediated by the long non-coding RNA HOTAIR inhibits the proliferation and invasion of glioma cells

Chen¹,

Bian²,

Zhao³

et al. 2016

Oncology Letters

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Abstract. Programmed cell death protein 4 (PDCD4) has recently been demonstrated to be implicated in translation and transcription, and the regulation of cell growth. However, the mechanisms underlying PDCD4 function in glioma cells remain to be elucidated. The current study investigated the function and regulation of PDCD4 and the results demonstrated that the expression of PDCD4 was significantly reduced in glioma cells compared with normal cells. When PDCD4 was overexpressed in glioma cells, the proliferation rate and invasive capability of the cells greatly decreased, suggesting that PDCD4 functions as a tumor suppressor in this cell type. In addition, the histone modification status of the PDCD4 gene was analyzed, and chromatin immunoprecipitation assay identified a high density of histone 3 lysine 27 trimethylation on the promoter of PDCD4, which was associated with the long non-coding RNA, homeobox transcript antisense RNA (HOTAIR). The expression of HOTAIR was significantly increased in glioma cells compared with normal cells, and it exerted its function in a polycomb repressive complex 2-dependent manner. These results may provide novel approaches to therapeutically target PDCD4 and HOTAIR in patients with gliomas. IntroductionHuman gliomas are the most prevalent malignant neoplasms of the central nervous system, with an annual incidence of ~5/100,000 worldwide (1). Despite the use of aggressive surgery in combination with chemotherapy, biological therapy and radiotherapy, gliomas continue to be therapeutically challenging (2). For patients with glioblastoma, the relative 5-year survival rate is <5% (3). Novel therapies for the treatment of glioma are warranted; recent advances in the understanding of the molecular and biological nature of this disease may facilitate the development of successful therapeutics (4).PDCD4 protein was initially determined to be overexpressed during apoptosis, which subsequently suppresses tumorigenesis (5,6). Loss of PDCD4 expression is closely associated with the progression of a number of tumors, including glioblastomas (7), and kidney, ovarian and lung cancer (8-10). Low PDCD4 expression levels correlate with poor outcomes in patients with glioblastoma multiforme (11). The frequent loss of PDCD4 in glioblastoma multiforme is partly due to epigenetic silencing secondary to 5' cytosine-phosphate-guanine island methylation (12), in addition to overexpression of microRNA (miRNA)-21, which targets PDCD4 mRNA for degradation (13). Although several studies have examined PDCD4 in glioma, the detailed molecular mechanisms underlying the role of PDCD4 in glioma remain poorly understood.Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides, which are involved in various important events, including transcriptional, epigenetic and post-transcriptional regulation (14,15). A previous study profiled the lncRNA homeobox transcript antisense RNA (HOTAIR), and the results demonstrated that HOTAIR was closely correlated with poor prognosis, molecular ...

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“…Our previous studies also demonstrated that PDCD4 had an important role in the development of ovarian cancer [3][4][5] and glioma. 6,7 Recent studies show that PDCD4 is also involved in various inflammatory diseases. It has been reported that PDCD4-deficient mice are resistant to streptozotocin-induced type II diabetes and experimental autoimmune encephalomyelitis, 8 and are also protected from the lethality of lipopolysaccharide (LPS).…”

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confidence: 99%

The inhibitory action of PDCD4 in lipopolysaccharide/D-galactosamine-induced acute liver injury

Wang

Zhang

Wei

et al. 2013

Laboratory Investigation

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Programmed cell death 4 (PDCD4) acts as a tumor suppressor gene, which suppresses tumor growth, infiltration and metastasis. Our previous studies demonstrated that PDCD4 had an important role in the development of ovarian cancer and glioma. Recent studies show that PDCD4 is also involved in various inflammatory diseases. However, its exact effect on inflammation remains unclear. In our current study, we explored the role of PDCD4 in acute liver injury induced by lipopolysaccharide (LPS) and D-galactosamine (D-GalN) using wild-type (WT) mice and PDCD4-deficient mice. Our results showed that liver-to-body weight ratios, as well as serum aspartate transaminase (AST) and alanine transaminase (ALT) levels were significantly increased in PDCD4-deficient mice than WT mice. Histological examination, immunohistochemical and TUNEL analysis revealed PDCD4-deficient mice had more necrotic and apoptotic hepatocytes, inflammatory cells infiltration and liver internal hemorrhage than WT mice. In addition, some inflammatory cytokines such as tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6) in the serum and liver tissues were also significantly increased in PDCD4-deficient mice. More importantly, we found that the aggravation of liver tissue injury in PDCD4-deficient mice was due to excessive mitogen-activated protein kinase and NF-kB activation, which induced the release of more inflammatory factors, and consequently resulted in higher levels of hepatocyte necrosis and apoptosis. These results indicate that PDCD4 has a protective role in LPS/D-GalN-induced acute liver injury. This finding may present new opportunities for PDCD4 to be explored as a therapeutic target in acute liver injury.

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

Cited by 63 publications

References 38 publications

Expression patterns of the tumor suppressor PDCD4 and correlation with β-catenin expression in gastric cancers

Expression patterns of the tumor suppressor PDCD4 and correlation with β-catenin expression in gastric cancers

Suppression of PDCD4 mediated by the long non-coding RNA HOTAIR inhibits the proliferation and invasion of glioma cells

The inhibitory action of PDCD4 in lipopolysaccharide/D-galactosamine-induced acute liver injury

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