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下调 GAS5 促进膀胱癌细胞增殖,部分通过调节 CDK6。

Downregulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6.

机构信息

Department of Urology, Shanghai First People's Hospital, Medical College of Shanghai Jiao Tong University, Shanghai, China.

出版信息

PLoS One. 2013 Sep 17;8(9):e73991. doi: 10.1371/journal.pone.0073991. eCollection 2013.

Abstract

UNLABELLED

Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as transcriptional regulation, cell growth and tumorigenesis. However, little is known about whether lncRNA-GAS5 (growth arrest-specific 5) regulates bladder cancer progression. In the present study, we found that the GAS5 expression is commonly downregulated in bladder cancer cell lines and human specimens. Knockdown of GAS5 promotes bladder cancer cell proliferation, whereas forced expression of GAS5 suppresses cell proliferation. We further demonstrated that knockdown of GAS5 increases CDK6 mRNA and protein levels in bladder cancer cells. Expectedly, GAS5 inhibition induces a significant decrease in G0/G1 phase and an obvious increase in S phase. Gain-of-function and loss-of-function studies showed that GAS5 inhibits bladder cancer cell proliferation, at least in part, by regulating CDK6 expression.

CONCLUSIONS

Downregulated GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6, and thus may be helpful in the development of effective treatment strategies against bladder cancer.

摘要

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长非编码 RNA(lncRNA)在多种生物过程中发挥重要作用,如转录调控、细胞生长和肿瘤发生。然而,lncRNA-GAS5(生长停滞特异性 5)是否调节膀胱癌进展知之甚少。在本研究中,我们发现 GAS5 在膀胱癌细胞系和人标本中普遍下调。GAS5 的敲低促进膀胱癌细胞增殖,而 GAS5 的强制表达则抑制细胞增殖。我们进一步证明,GAS5 的敲低增加了膀胱癌细胞中 CDK6 mRNA 和蛋白水平。预期的是,GAS5 抑制导致 G0/G1 期明显减少,S 期明显增加。功能获得和功能丧失研究表明,GAS5 通过调节 CDK6 的表达抑制膀胱癌细胞增殖,至少部分如此。

结论

下调的 GAS5 促进膀胱癌细胞增殖,部分通过调节 CDK6,因此可能有助于开发针对膀胱癌的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e233/3775789/dda003f211fd/pone.0073991.g001.jpg

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