MiR-219a-2-3p suppresses cell proliferation and promotes apoptosis by targeting MDM2/p53 in pituitary adenomas cells

Biosci Biotechnol Biochem. 2020 May;84(5):911-918. doi: 10.1080/09168451.2020.1715780. Epub 2020 Jan 20.

Abstract

Pituitary adenomas constitute one of the most common intracranial tumors. MicroRNAs play an important role in development and progression of pituitary adenomas. In this study, we showed that miR-219a-2-3p was significantly down-regulated in pituitary adenomas cells. Overexpression of miR-219a-2-3p suppressed the proliferation and promoted apoptosis of pituitary adenomas cells. After bioinformatics analysis, we found that MDM2 was one of the downstream targets of miR-219a-2-3p. Further researches showed that miR-219a-2-3p could reduce the protein level of MDM2 by binding to the 3'-UTR of MDM2 and promoted p53 expression. Then, we overexpressed both miR-219a-2-3p and MDM2 in the same group and found that it could counteract the effect of overexpressing miR-219a-2-3p alone on proliferation and apoptosis of pituitary adenoma cells. Taken together, these results suggested that miR-219a-2-3p regulated the proliferation and apoptosis by targeting MDM2/p53 in pituitary adenomas. Therefore, miR-219a-2-3p may serve as a novel marker and therapeutic target for pituitary adenomas.

Keywords: MDM2; apoptosis; miR-219a-2-3p; p53; proliferation.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Animals
  • Apoptosis / genetics*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Pituitary Neoplasms / metabolism*
  • Pituitary Neoplasms / pathology
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Signal Transduction / genetics*
  • Transfection
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Trp53 protein, mouse
  • Tumor Suppressor Protein p53
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2