miR-193b-3p possesses anti-tumor activity in ovarian carcinoma cells by targeting p21-activated kinase 3

Biomed Pharmacother. 2017 Dec:96:1275-1282. doi: 10.1016/j.biopha.2017.11.086. Epub 2017 Nov 21.

Abstract

miR-193b-3p was found to be downregulated and contributed to ovarian cancer (OC) progression. In the present study, we aimed to study the detailed role of miR-193b-3p in the development of OC and the underlying molecular mechanism. The results showed that miR-193b-3p was downregulated while PAK3 was upregulated in OC cells. Ectopic expression of miR-193b-3p and PAK3 knockdown repressed cell proliferation, promoted paclitaxel-induced cytotoxicity, and reinforced paclitaxel-mediated caspase-3 activity increase in OC cells. Notably, miR-193b-3p was identified to directly target PAK3 and suppressed PAK3 expression. Moreover, enforced expression of PAK3 partially overturned the effects of miR-193b-3p on OC cell proliferation and paclitaxel sensitivity. In conclusion, miR-193b-3p possessed anti-tumor activity in OC through inhibiting cell proliferation and enhancing paclitaxel sensitivity by targeting PAK3. Therefore, our study suggested that the miR-193b-3p/PAK3 axis might be a potential novel therapeutic target for OC.

Keywords: Ovarian carcinoma; PAK3; Paclitaxel sensitivity; Proliferation; miR-193b-3p.

MeSH terms

  • Caspase 3 / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Down-Regulation / drug effects
  • Down-Regulation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Paclitaxel / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • p21-Activated Kinases / genetics*

Substances

  • MIRN193 microRNA, human
  • MicroRNAs
  • PAK3 protein, human
  • p21-Activated Kinases
  • Caspase 3
  • Paclitaxel