MiR-616-3p promotes angiogenesis and EMT in gastric cancer via the PTEN/AKT/mTOR pathway

Biochem Biophys Res Commun. 2018 Jul 2;501(4):1068-1073. doi: 10.1016/j.bbrc.2018.05.109. Epub 2018 May 21.

Abstract

Dysregulation of microRNAs has been demonstrated to be involved in a variety of biological events related to cancer, including proliferation, metastasis, angiogenesis and immune escape. MiR-616-3p is located on the chromosome region 12q13.3, however, its potential role and clinical implications in gastric cancer remain poorly understood. The current study aimed to investigate the potential role of miR-616-3p in gastric cancer. The results showed that miR-616-3p was up-regulated in cancer tissues. Higher expression of miR-616-3p in tumor tissues also predicted poor prognosis. Furthermore, loss- and gain-of-function in vitro revealed that miR-616-3p promoted angiogenesis and EMT in gastric cancer cells. Mechanistically, further analysis demonstrated that the effects of miR-616-3p on metastasis and angiogenesis occurred through the down-regulation of PTEN, a direct target of miR-616-3p. We propose that the restoration of PTEN expression may block miR-616-3p-induced EMT and angiogenesis. Collectively, our findings suggest that the miR-616-3p-PTEN signaling axis might be a potential therapeutic target for gastric cancer.

Keywords: Angiogenesis; EMT; Gastric cancer; Metastasis; MiR-616-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Epithelial-Mesenchymal Transition / genetics*
  • Gene Expression Regulation, Neoplastic
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / genetics*
  • PTEN Phosphohydrolase / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Stomach Neoplasms / blood supply*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology
  • TOR Serine-Threonine Kinases / metabolism*
  • Up-Regulation / genetics

Substances

  • MIRN616 microRNA, human
  • MicroRNAs
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human