MicroRNA-485-5p reduces O-GlcNAcylation of Bmi-1 and inhibits colorectal cancer proliferation

Exp Cell Res. 2018 Jul 1;368(1):111-118. doi: 10.1016/j.yexcr.2018.04.020. Epub 2018 Apr 20.

Abstract

Emerging evidences showed that miRNAs are involved in the oncogenesis of many cancers. Here, miRNA microarray analysis was performed to screen the significant miRNAs involved in the progression of colorectal cancer (CRC), miR-485-5p was chosen for further study. We found that the expression of miR-485-5p was significantly lower in CRC specimens and cell lines. In addition, low expression level of miR-485-5p is correlated with tumor progression and poor survival in CRC patients. Based on in vitro and in vivo assays, we found that miR-485-5p significantly inhibits CRC proliferation. Moreover, our results showed that miR-485-5p inhibits cell proliferation by reducing Bmi-1 protein expression, which has been reported to control the proliferation of many cancers. Mechanistically, OGT is a direct target of miR-485-5p, and miR-485-5p could inhibit the O-GlcNAcylation level of Bmi-1 by OGT. Overall, these results suggested that as a tumor suppressor, miR-485-5p may regulate CRC cells proliferation, which could regulate the O-GlcNAcylation and the stability of Bmi-1 through targeting OGT. This may give insight into a novel mechanism and therapy of CRC growth.

Keywords: Bmi-1; Colorectal cancer; OGT; Proliferation; miR-485-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • MicroRNAs / genetics*
  • Polycomb Repressive Complex 1 / genetics*

Substances

  • BMI1 protein, human
  • MIRN485 microRNA, human
  • MicroRNAs
  • Polycomb Repressive Complex 1