MicroRNA-203 inhibits epithelial-mesenchymal transition, migration, and invasion of renal cell carcinoma cells via the inactivation of the PI3K/AKT signaling pathway by inhibiting CAV1

Cell Adh Migr. 2020 Dec;14(1):227-241. doi: 10.1080/19336918.2020.1827665.

Abstract

The present study aimed to evaluate the underlying mechanism of microRNA-203 (miR-203) in renal cell carcinoma (RCC) involving the PI3K/AKT signaling pathway. The results revealed downregulated miR-203 and upregulated CAV1 in RCC tissues. Upregulated miR-203 and downregulated CAV1 increased E-cadherin expression and cell apoptosis, decreased β-catenin and N-cadherin expression and cell proliferation, migration and invasion, and blocked cell cycle entry. CAV1, a target gene of miR-203, decreased by up-regulated miR-203, and silencing CAV1 led to the inactivation of PI3K/AKT signaling pathway. In conclusion, our findings suggested that miR-203-mediated direct suppression of CAV1 inhibits EMT of RCC cells via inactivation of the PI3K/AKT signaling pathway.

Keywords: CAV1; MicroRNA-203; PI3K/AKT signaling; apoptosis; epithelial-mesenchymal transformation; invasion; migration; proliferation; renal cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Apoptosis / genetics
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / pathology*
  • Caveolin 1 / antagonists & inhibitors*
  • Caveolin 1 / metabolism
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement* / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Silencing
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Invasiveness
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Up-Regulation / genetics
  • Young Adult

Substances

  • Caveolin 1
  • MIRN203 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-akt