MiR-139 Induces an Interferon-β Response in Prostate Cancer Cells by Binding to RIG-1

Cancer Genomics Proteomics. 2021 May-Jun;18(3):197-206. doi: 10.21873/cgp.20252.

Abstract

Background: We previously identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. Expression of one of the down-regulated miRNAs, miR-139-5p, was significantly associated with a lower incidence of biochemical recurrence and metastasis. Transcriptome profiling of miR-139-expressing prostate cancer cells revealed up-regulation of genes involved in interferon (IFN) stimulation. The association between miR-139 and IFN-β was further explored in this study.

Materials and methods: We examined miR-139 transfected PC3, Du145 and LNCaP cells and the associated IFN response by transcriptome sequencing, immunoblotting and pulldown assays.

Results: Treatment of prostate cancer cells by miR-139 resulted in the up-regulation of IFN-related genes. Specifically, miR-139 induced expression of the IFN-β protein. The ability of miR-139 to induce IFN-β was due to its binding to RIG-1 and the induction of IFN-related genes was found to be dependent on RIG-1 expression.

Conclusion: miR-139 acts as an immune agonist of RIG-1 to enhance IFN-β response in prostate cancer cells.

Keywords: NGS; RIG-1; interferon; microRNA; prostate cancer; transcriptome.

MeSH terms

  • Cell Line, Tumor
  • DEAD Box Protein 58 / immunology
  • DEAD Box Protein 58 / metabolism*
  • HEK293 Cells
  • Humans
  • Interferon-beta / biosynthesis*
  • Interferon-beta / genetics
  • Interferon-beta / immunology
  • Male
  • MicroRNAs / administration & dosage
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • PC-3 Cells
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / therapy
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Signal Transduction
  • Transfection
  • Up-Regulation

Substances

  • MIRN139 microRNA, human
  • MicroRNAs
  • Receptors, Immunologic
  • Interferon-beta
  • RIGI protein, human
  • DEAD Box Protein 58