GAS5 Inhibits Gastric Cancer Cell Proliferation Partly by Modulating CDK6

Oncol Res Treat. 2015;38(7-8):362-6. doi: 10.1159/000433499. Epub 2015 Jul 1.

Abstract

Introduction: As it is not clear whether growth arrest-specific 5 (GAS5) inhibits gastric cancer (GC) cell proliferation by regulating cell cycle, we analyzed the effect of GAS5 on cell cycle regulation of GC cells and explored the underlying mechanism.

Methods: We measured GAS5 levels in GC tissues and corresponding normal tissues, and analyzed the role of GAS5 in regulation of cell proliferation and cell cycle in GC cells using CCK-8 assay and flow cytometry. We also measured the expression of P21 and CDK6 proteins after transfection of AGS and MGC-803 cells with pLJM-GAS5 and GAS5 siRNA, respectively, by western blotting.

Results: GAS5 expression was significantly lower in GC tissues relative to normal tissues, and its lower expression was correlated with larger tumor size and a more advanced clinical stage of GC. GAS5 induced growth arrest of GC cells through inhibition of G1-S phase translation. The action of GAS5 may be mediated by upregulation of P21 and suppression of CDK6.

Conclusion: These data enhance our understanding of the important role that GAS5 plays in the molecular etiology of GC and suggest a potential of GAS5 as a new therapeutic target for GC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Proteins / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology*

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • GAS5 long non-coding RNA, human
  • Neoplasm Proteins
  • RNA, Long Noncoding
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 6