miR-197-3p Represses the Proliferation of Prostate Cancer by Regulating the VDAC1/AKT/β-catenin Signaling Axis

Int J Biol Sci. 2020 Feb 21;16(8):1417-1426. doi: 10.7150/ijbs.42019. eCollection 2020.

Abstract

Accumulating investigations have demonstrated that microRNAs (miRNAs) are promising efficient targets for the next generation of molecular therapeutics. The development of miRNA-based therapies requires the identification and validation of cancer-associated miRNAs. Herein, we identified that miR-197-3p regulates the carcinogenesis and development of prostate cancer (PCa) via bioinformatics analysis. Next, we investigated the function and regulatory mechanisms of miR-197-3p in PCa. Overexpression of miR-197-3p suppressed PCa cell proliferation and colony formation. In contrast, inhibition of miR-197-3p activity enhanced PCa cell proliferation and colony formation. Mechanistic investigations identified that voltage dependent anion channel 1 (VDAC1) is a direct target of miR-197-3p. miR-197-3p targeting of VDAC1 resulted in downregulation of p-Akt and β-catenin. Subsequently, we found that restoration of VDAC1 abolished the effects of miR-197-3p on PCa cell proliferation and AKT signaling pathway. Furthermore, we confirmed that miR-197-3p suppressed tumor xenograft growth in vivo. In conclusion, our study offers an empirical investigation of miR-197-3p, a tumor suppressor that may be a potential therapeutic target in PCa.

Keywords: AKT; VDAC1; miR-197-3p; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation
  • Computational Biology
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / metabolism*
  • Neoplasm Transplantation
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction
  • Voltage-Dependent Anion Channel 1 / metabolism*
  • Wnt Signaling Pathway
  • beta Catenin / metabolism*

Substances

  • CTNNB1 protein, mouse
  • MIRN197 microRNA, human
  • MicroRNAs
  • VDAC1 protein, human
  • Vdac1 protein, mouse
  • beta Catenin
  • Voltage-Dependent Anion Channel 1
  • Akt1 protein, mouse
  • Proto-Oncogene Proteins c-akt