microRNA-183-3p Inhibits Progression of Human Prostate Cancer by Downregulating High-Mobility Group Nucleosome Binding Domain 5

DNA Cell Biol. 2019 Aug;38(8):840-848. doi: 10.1089/dna.2019.4642. Epub 2019 Jul 17.

Abstract

microRNAs are a class of noncoding RNAs that play important roles in cancer progression. microRNA-183-3p (miR-183-3p) is a novel microRNA that is dysregulated in many kinds of cancers. Our previous studies found high expression and oncologic role of high-mobility group nucleosome binding domain 5 (HMGN5) in prostate cancer. In this study, we found that miR-183-3p was downregulated in prostate cancer cells and primary tissues compared with normal controls. In addition, miR-183-3p expression was negatively correlated with HMGN5 expression. On the basis of bioinformatics predication and quantitative polymerase chain reaction and Western blot verification, it is demonstrated that miR-183-3p regulated HMGN5 expression. Luciferase reporter assay confirmed that miR-183-3p directly targeted the 3'-untranslated region of HMGN5. Interestingly, cell proliferation and migration inhibition and apoptosis induction were also observed in miR-183-3p transfected human prostate cancer VCap and C4-2 cells. Moreover, overexpression of HMGN5 significantly reversed the inhibitory effect on cell proliferation and migration and promoted effect on cell apoptosis by miR-183-3p. Our data suggest that dysfunction of miR-183-3p-HMGN5 axis plays an oncogenic role and can be a therapeutic target for prostate cancer.

Keywords: HMGN5; microRNA-183-3p; prostate cancer.

MeSH terms

  • 3' Untranslated Regions
  • Aged
  • Apoptosis / genetics
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • HMGN Proteins / genetics*
  • HMGN Proteins / metabolism
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Trans-Activators / genetics*
  • Trans-Activators / metabolism

Substances

  • 3' Untranslated Regions
  • HMGN Proteins
  • HMGN5 protein, human
  • MIRN183 microRNA, human
  • MicroRNAs
  • Trans-Activators