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

• Published in: PloS one Vol. 8; no. 9; p. e73991
• Main Authors: Liu, Zhihong, Wang, Wei, Jiang, Juntao, Bao, Erdun, Xu, Dongliang, Zeng, Yigang, Tao, Le, Qiu, Jianxin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.09.2013; Public Library of Science (PLoS)
• Subjects: Aged; Apoptosis; Biological activity; Bladder; Bladder cancer; Breast cancer; Cancer; Cell cycle; Cell Cycle - genetics; Cell growth; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase 6 - genetics; Cyclin-Dependent Kinase 6 - metabolism; Development and progression; Female; G1 phase; Gene expression; Gene Expression Regulation, Neoplastic; Gene regulation; Genomes; Hospitals; Humans; Kinases; Male; Metastasis; Middle Aged; Neoplasm Grading; Neoplasm Staging; RNA; RNA Interference; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; S phase; Transcription; Transcription (Genetics); Tumor cell lines; Tumorigenesis; Tumors; Urinary bladder; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urology; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0073991

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. 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.