miR-451a is downregulated and targets PSMB8 in prostate cancer

Kaohsiung J Med Sci. 2020 Jul;36(7):494-500. doi: 10.1002/kjm2.12196. Epub 2020 Mar 3.

Abstract

Abnormal expression of microRNAs (miRNAs) is frequently occurred in prostate cancer (PCa). This study was aimed to investigate the biological roles of miR-451a in PCa. Quantitative real-time PCR (qRT-PCR) and Western blot were employed to investigate the expression levels of miR-451a and proteasome (prosome, macropain) subunit, beta type, 8 (PSMB8) in PCa cell lines. Luciferase activity reporter assay was used to verify the connection between miR-451a and PSMB8. in vitro functional experiments were performed to measure the effects of miR-451a or PSMB8 on PCa cell proliferation, colony formation ability, cell invasion, and cell apoptosis. miR-451a expression was downregulated, whereas PSMB8 expression was upregulated in PCa cell lines. Luciferase activity reporter assay confirmed the direct connection between miR-451a and PSMB8. Overexpression of miR-451a inhibits PCa cell proliferation, colony formation, cell invasion and promotes cell apoptosis, while the overexpression of PSMB8 caused the opposite effects. Moreover, rescue experiments confirmed PSMB8 was a functional target of miR-451a. In conclusion, this study provides novel insights into the role of miR-451a in PCa, and the results demonstrated miR-451a could inhibit PCa progression by targeting PSMB8.

Keywords: PSMB8; cell invasion; cell proliferation; colony formation; miR-451a; prostate cancer.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Apoptosis / genetics
  • Base Pairing
  • Base Sequence
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Humans
  • Luciferases / genetics
  • Luciferases / metabolism
  • Male
  • MicroRNAs / agonists
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Mimicry
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Prostate / metabolism*
  • Prostate / pathology
  • Proteasome Endopeptidase Complex / genetics*
  • Proteasome Endopeptidase Complex / metabolism
  • Signal Transduction

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • MIRN451 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • Luciferases
  • LMP7 protein
  • Proteasome Endopeptidase Complex