miR-484 is associated with disease recurrence and promotes migration in prostate cancer

Biosci Rep. 2020 May 29;40(5):BSR20191028. doi: 10.1042/BSR20191028.

Abstract

Background: microRNAs (miRs) regulate the expression of protein-coding genes and play key roles in various biological processes, including development and immunity. However, dysregulation of miR expression is also involved in disease biology, including cancer.

Methods: We utilized The Cancer Genome Atlas (TCGA) and other publicly available databases for miRs and mRNA expression in prostate cancer, selected miR-484 and investigated its role in prostate cancer biology and disease progression using in vitro studies.

Results: Our data mining efforts revealed that increased miR-484 in prostate tumors associates with early disease recurrence, while miR-484 expression in human prostate cancer cells enhances cancer cell mobility. Using RNAseq and bioinformatics, we identified candidate target genes of miR-484 and generated a list of potential tumor suppressors. One candidate in this list was PSMG1. We applied luciferase assays and immunoblotting to confirm that miR-484 directly targets PSMG1. Additional in vitro assays with cancer cell lines showed that PSMG1 knockdown rescued the reduction in mobility brought on by miR-484 inhibition, pointing toward the existence of a miR-484-PSMG1 axis in prostate cancer.

Conclusions: We hypothesize that miR-484 is an oncogene in the prostate that increases cancer cell mobility, with PSMG1 being a mir-484 target in this process.

Keywords: microRNA; oncogenesis; prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Computational Biology
  • Datasets as Topic
  • Disease-Free Survival
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Knockdown Techniques
  • Humans
  • Male
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / metabolism*
  • Molecular Chaperones / genetics*
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Prostate / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • RNA-Seq
  • Up-Regulation

Substances

  • MIRN484 microRNA, human
  • MicroRNAs
  • Molecular Chaperones
  • PSMG1 protein, human