MiR-422a targets MAPKK6 and regulates cell growth and apoptosis in colorectal cancer cells

Biomed Pharmacother. 2018 Aug:104:832-840. doi: 10.1016/j.biopha.2018.03.013. Epub 2018 Mar 19.

Abstract

The important role of miR-422a in tumor has been reported in several studies. Recent research discovered that the expression of miR-422a was significantly decreased in colorectal cancer tissues, providing miR-422a as a tumor suppressor in CRC. However, the concrete mechanism of miR-422a regulating CRC cell is still unclear. In this study, we demonstrated that miR-422a could inhibit CRC cell growth and promote cell apoptosis via in vitro analyses. Moreover, computational methods were adopted to identify the targets of miR-422a. We found MAPKK6 was the direct target of miR-422a. Consequently, we further elucidated that miR-422a inhibited CRC cell growth and induced cell apoptosis by inhibiting p38/MAPK pathway. Besides that, we established the tumor xenograft model using nude mice and the inhibitory effects on tumor volumes and weights by miR-422a mimic transfection were also detected. Taken together, these findings demonstrated miR-422a exerted anti-cancer activities on CRC, which could be potentially used for CRC prognosis prediction and treatment.

Keywords: Apoptosis; Cell growth; Colorectal cancer; miRNA; p38.

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology*
  • Female
  • Genes, Tumor Suppressor / physiology
  • HCT116 Cells
  • Humans
  • MAP Kinase Kinase 6 / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Middle Aged
  • Prognosis
  • p38 Mitogen-Activated Protein Kinases / genetics

Substances

  • MIRN422 microRNA, human
  • MicroRNAs
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 6