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

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

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase 6 / genetics*
  • Cyclin-Dependent Kinase 6 / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • RNA Interference
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • GAS5 long non-coding RNA, human
  • RNA, Long Noncoding
  • Cyclin-Dependent Kinase 6

Grants and funding

This work was supported by the Award Number XBR 2011038 from Shanghai Municipal Health Bureau. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.