Primate-specific miR-944 activates p53-dependent tumor suppression in human colorectal cancers

Cancer Lett. 2019 Jan:440-441:168-179. doi: 10.1016/j.canlet.2018.10.029. Epub 2018 Oct 27.

Abstract

As cancers with a high incidence rate, colorectal cancers are a main cause of cancer-related death. MicroRNAs are often deregulated in cancers. The primate-specific miR-944, located in a p63 intron, is known to be highly expressed in patients exhibiting low colorectal cancer recurrence rates. However, the biological functions of miR-944 in colorectal cancers remain unclear. In this study, we found that miR-944 was downregulated in colorectal cancer tissues, and inhibited cancer cell growth in a xenograft mouse model. The overexpression of miR-944 caused G1 phase arrest and increased p53 expression in cancer cells. p53 stability was enhanced by miR-944s targeting E3 ligases COP1 and MDM2. Overexpression of COP1 and MDM2 restored cell growth inhibition caused by miR-944. Taken together, our results suggest that miR-944 acts as a potential tumor suppressor in colorectal cancers through the ubiquitin-proteasome system.

Keywords: Colorectal cancer; Primate specific miRNA; Tumor suppressor; miR-944; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • HCT116 Cells
  • HT29 Cells
  • Heterografts
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Proto-Oncogene Proteins c-mdm2 / genetics
  • Proto-Oncogene Proteins c-mdm2 / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • MIRN-944 microRNA, human
  • MicroRNAs
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • COP1 protein, human
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Ubiquitin-Protein Ligases