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Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1.

ABSTRACT: Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased cleaved caspase-3 and cleaved PARP. PVT1 increased Mcl-1 mRNA levels in renal cancer cells by promoting mRNA stability without influencing its transcription. in vitro, the enhanced apoptosis arising from PVT1 suppression was attenuated by overexpressing Mcl-1. In addition, in vivo experiments showed that PVT1 knockdown repressed xenograft tumor growth, while Mcl-1 overexpression partially rescued xenograft tumor growth. These results indicate the PVT1/Mcl-1 pathway inhibits renal cancer cell apoptosis in vitro and in vivo. PVT1 may thus serve as a novel biomarker, and the PVT1/Mcl-1 pathway may be a useful therapeutic target for clear cell renal cell carcinoma.

SUBMITTER: Wu Q

PROVIDER: S-EPMC5731919 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1.

Wu Qingjian Q Yang Fan F Yang Zhenxing Z Fang Zhenqiang Z Fu Wanlei W Chen Wei W Liu Xiaobing X Zhao Jiang J Wang Qingqing Q Hu Xiaoyan X Li Longkun L

Oncotarget 20171009 60

Long non-coding RNA plasmacytoma variant translocation 1 (PVT1) is up-regulated in various human cancers, and our results indicated that PVT1 was up-regulated in clear cell renal cell carcinoma tissues. The Cancer Genome Atlas cohort analysis revealed that in clear cell renal cell carcinoma, higher PVT1 expression correlated with advanced TNM stage, histological grade, and poor survival. PVT1 knockdown promoted apoptosis, inhibited renal cancer cell proliferation, decreased Mcl-1, and increased ...[more]

PMID: 29254209

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Project description:ObjectiveIn this study, we aimed to clarify the effects of long noncoding ribonucleic acid prostrate androgen-regulated transcript-1 on bladder cancer cell proliferation and apoptosis.MethodsMicroarrays were implemented to investigate the long noncoding ribonucleic acid expression profiles in bladder cancer tissue (N = 9) and in noncancer bladder tissue (N = 5). Relative prostrate androgen-regulated transcript-1 expression levels in tissue samples or cell lines were detected by real-time quantitative reverse transcription-polymerase chain reaction. Prostrate androgen-regulated transcript-1 expression was enhanced by the transfection of pcDNA3.1-prostrate androgen-regulated transcript-1 and downregulated by the infection with pcMV-sh prostrate androgen-regulated transcript-1. Additionally, cell proliferation and apoptosis were measured by the cell counting kit-8 assay and flow cytometry, respectively. Cell invasion was determined by a Transwell assay.ResultsProstrate androgen-regulated transcript-1 expression was upregulated in bladder cancer tissues compared to adjacent nontumor tissues. Furthermore, prostrate androgen-regulated transcript-1 levels were successfully upregulated by pcDNA3.1-prostrate androgen-regulated transcript-1 and depleted by pCMV-sh prostrate androgen-regulated transcript-1 in bladder cancer cell lines (5637, T24). Enhanced prostrate androgen-regulated transcript-1 expression promoted cell proliferation and invasion and inhibited cell apoptosis. However, knockdown of prostrate androgen-regulated transcript-1 expression inhibited cell proliferation and invasion and induced cell apoptosis.ConclusionIn summary, these data suggest that the knockdown of prostrate androgen-regulated transcript-1 represents a tumor suppressor player in bladder cancer and contributes to the inhibition of tumor proliferation, the promotion of cell apoptosis, and the suppression of cell invasion. Prostrate androgen-regulated transcript-1 may function as a new prognostic biomarker and as a feasible therapeutic target for patients with bladder cancer.

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Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1.

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Long noncoding RNA PVT1 inhibits renal cancer cell apoptosis by up-regulating Mcl-1.

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