MiR-206 inhibits epithelial ovarian cancer cells growth and invasion via blocking c-Met/AKT/mTOR signaling pathway

Biomed Pharmacother. 2018 Aug:104:763-770. doi: 10.1016/j.biopha.2018.05.077. Epub 2018 May 29.

Abstract

Background: MicroRNAs play important roles in the pathogenesis of various kinds of tumors. However, there are few studies on the expression profile and function of miRNAs in epithelial ovarian cancer. In this study, we performed microRNA array to compare the expression profile of microRNA in ovarian cancer tissues with noncancerous tissues.

Methods: qRT-PCR was used to further confirm the microRNA expression levels in epithelial ovarian cancer tissues and cell lines. The function of microRNA was analyzed by overexpressing microRNA mimics followed by the analysis of cell cycle, proliferation, and metastasis. The downstream target of miR-206 was found and western blot analysis was performed to measure the activation of the downstream signaling pathway.

Results: In this study, we found the expression of miR-206 was significantly down-regulated in epithelial ovarian cancer tissues and epithelial ovarian cancer cell lines. In epithelial ovarian cancer patients, downregulation of miR-206 was associated with metastasis and poor prognosis. In epithelial ovarian cancer cell lines, miR-206 contributed to the cell cycle regulation, cell apoptosis, and cancer cell metastasis. MiR-206 mimics inhibited cancer cell proliferation and metastasis, and induced cell apoptosis. Moreover, our results demonstrated that miR-206 directly targeted c-Met and repressed the activation of downstream AKT/mTOR signaling pathway.

Conclusion: Our results demonstrated that miR-206 was down-regulated in epithelial ovarian cancer tissues and cell lines. MiR-206 inhibits the development of epithelial ovarian cancer cell by directly targeting c-Met and inhibiting the c-Met/AKT/mTOR signaling pathway.

Keywords: AKT/mTOR; Epithelial ovarian cancer; MiR-206; MicroRNA profiling; c-Met.

MeSH terms

  • Apoptosis / genetics
  • Carcinoma, Ovarian Epithelial
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-met / genetics*
  • Signal Transduction / genetics*
  • TOR Serine-Threonine Kinases / genetics*

Substances

  • MIRN206 microRNA, human
  • MicroRNAs
  • MTOR protein, human
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases