Upregulation of miR-191 promotes cell growth and invasion via targeting TIMP3 in prostate cancer

J BUON. 2018 Mar-Apr;23(2):444-452.

Abstract

Purpose: Prostate cancer (PCa) is the most frequently malignant neoplasm in men. MicroRNAs (miRs) have been identified to play important biological roles in a variety of tumors. Several studies showed that miR-191 was involved in the development of different cancers, but its role in prostate cancer remains unclear.

Methods: Human PCa cell lines DU145, PC-3 and LNCAP, and benign prostate hyperplasia (BPH) and human prostate epithelial cell line RWPE-1 were used. The expression level of miR-191 in 48 paired prostate tumor and adjacent normal tissues was assessed along with the clinical patient features. Synthetic miR-191 mimics and inhibitors were used to overexpress or inhibit the miR-191 level. CCK8 and colony formation assay were used to evaluate the cell growth. The ability of cell invasion was studied by transwell assay. Dual-luciferase experiment was used to identify the target gene and western blot was performed to evaluate the protein level.

Results: miR-191 was overexpressed in PCa tissue samples compared to the normal group as well in PCa-derived cell lines. Upregulation miR-191 in PC-3 cells significantly promoted while downregulation miR-191 in DU145 cells retarded the cell proliferation and invasion. Furthermore, TIMP3 were proved to be a direct target gene of miR-191 and knockdown of TIMP3 reversed the function of miR-191 downregulation.

Conclusion: This study demonstrated that miR-191 promoted the cell growth and invasion ability in prostate cancer through downregulating TIMP3 and might be a potential target for the biotherapy for PCa.

MeSH terms

  • Aged
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Prostate
  • Prostatic Hyperplasia / genetics*
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Tissue Inhibitor of Metalloproteinase-3 / genetics*

Substances

  • MIRN191 microRNA, human
  • MicroRNAs
  • TIMP3 protein, human
  • Tissue Inhibitor of Metalloproteinase-3