MicroRNA‑495 regulates human gastric cancer cell apoptosis and migration through Akt and mTOR signaling

Oncol Rep. 2018 Dec;40(6):3654-3662. doi: 10.3892/or.2018.6722. Epub 2018 Sep 21.

Abstract

In the present study, we investigated the expression and cellular distribution of microRNA‑495 (miR‑495) in human gastric cancer. Prominent downregulation of miR‑495 activation was evident in patients with gastric cancer. Cell viability and Annexin V/PI apoptosis assays were used to assess cell proliferation and apoptosis. Then, western blot analysis was used to assess cyclin D1, PI3K, p‑Akt and p‑mTOR protein expression. Overexpression of miR‑495 significantly inhibited cell proliferation, and promoted cell apoptosis of gastric cancer cells. Overexpression of miR‑495 also promoted caspase‑3/‑9 and Bax protein expression, and suppressed cyclin D1 protein expression and the PI3K/Akt/mTOR pathway in gastric cancer cells. Downregulation of miR‑495 increased cell proliferation and inhibited cell apoptosis of gastric cancer cells through activation of the PI3K/Akt/mTOR pathway. The PI3K inhibitor, was used to suppress the PI3K/Akt/mTOR pathway, inhibit cell proliferation, promote cell apoptosis, promote caspase‑3/‑9 and Bax protein expression, and suppress cyclin D1 protein expression of gastric cancer cells through miR‑495 inhibition. In conclusion, miR‑495 is an important regulator of human gastric cancer cells and may contribute to cell apoptosis through the PI3K/Akt/mTOR/Bax‑caspase‑3/‑9 and cyclin D1 pathway.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclin D1 / metabolism
  • Down-Regulation*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs / genetics*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / metabolism
  • Survival Analysis
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • CCND1 protein, human
  • MIRN495 microRNA, human
  • MicroRNAs
  • Cyclin D1
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases