MiR-106a-5p inhibits the cell migration and invasion of renal cell carcinoma through targeting PAK5

Cell Death Dis. 2017 Oct 26;8(10):e3155. doi: 10.1038/cddis.2017.561.

Abstract

MicroRNA-106a-5p (MiR-106a-5p), a small non-coding RNA, has been reported to be downregulated in astrocytoma, osteosarcoma and colorectal cancer. However, the expression levels and biological function in renal cell carcinoma (RCC) have not been studied yet. In this study, we found that the miR-106a-5p was significantly downregulated in RCC tissues and cell lines, and that overexpression of miR-106a-5p led to decreased cell metastasis ability in a xenograft model. Inhibition of miR-106a-5p in RCC cell lines altered the cell migration, invasion and wound healing abilities. Mechanistic studies demonstrated that miR-106a-5p directly bound to the 3'-UTR of the PAK5 mRNA and mediated a decrease in the protein expression of PAK5. We further proved that PAK5 protein levels were negatively correlated with the miR-106a-5p expression in both patient samples and xenograft model. In epigenetics, methylation specific PCR experiments indicated that the upstream gene promoter of miR-106a-5p was hypermethylated in RCC, which might be responsible for its downregulation. Our findings suggested that miR-106a-5p might be a potential gene therapy target for the treatment of RCC metastasis.

MeSH terms

  • Animals
  • Carcinoma, Renal Cell / enzymology
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Down-Regulation
  • Female
  • Humans
  • Kidney Neoplasms / enzymology
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Transfection
  • p21-Activated Kinases / genetics*
  • p21-Activated Kinases / metabolism

Substances

  • MIRN106 microRNA, human
  • MicroRNAs
  • PAK5 protein, human
  • p21-Activated Kinases