RASSF1A inhibits gastric cancer cell proliferation by miR-711- mediated downregulation of CDK4 expression

Oncotarget. 2016 Feb 2;7(5):5842-51. doi: 10.18632/oncotarget.6813.

Abstract

Although interaction with DNA repair proteins has demonstrated that RASSF1A is a tumour suppressor gene, much attention has been directed in recent years towards its roles in regulating the cell cycle. However, the precise mechanism remains unclear. Uncovering how RASSF1A participates in regulating the cell cycle is critical to exploring effective therapeutic targets for gastric cancer. Here we show that RASSF1A could regulate 14 miRNAs' expression in the typical human gastric cancer line SGC-7901, of which miR-711 was upregulated the most. Moreover, for SGC-7901 cells, miR-711 was found to downregulate CDK4 expression, and to arrest the cell cycle in the G1 phase. Our results suggest that RASSF1A inhibits the proliferation of gastric cancer cells by upregulating the expression of miR-711, which arrested gastric cancer cells in the G1 phase by downregulating expression of CDK4. This finding might provide us with a novel therapeutic target for gastric cancer by increasing RASSF1A expression via miR-711 regulation.

Keywords: CDK4; RASSF1A; cell cycle; gastric cancer; miR-711.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Western
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation*
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • MicroRNAs / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology*
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Wound Healing

Substances

  • MicroRNAs
  • RASSF1 protein, human
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4