MicroRNA 10a induces glioma tumorigenesis by targeting myotubularin-related protein 3 and regulating the Wnt/β-catenin signaling pathway

FEBS J. 2019 Jul;286(13):2577-2592. doi: 10.1111/febs.14824. Epub 2019 Apr 11.

Abstract

MicroRNAs are involved in the regulation of tumor formation. A previous study suggested that miR-10a promotes glioma cell migration and invasion. However, the effect of miR-10a on the proliferation of glioma cells remains unknown. In this study, we demonstrated that miR-10a promoted proliferation and reduced apoptosis in glioma cells by directly targeting the 3'-UTR of myotubularin-related protein 3 (MTMR3). miR-10a enhanced, while MTMR3 weakened, the growth of glioma in vivo. Ectopic expression of MTMR3 neutralized the effect of miR-10a on glioma. Furthermore, miR-10a and MTMR3 regulated β-catenin expression and genes downstream of the Wnt/β-catenin signaling pathway, such as Bcl-2, c-myc, p-c-Jun, and cleaved caspase-3, to affect the proliferation ability and apoptosis of glioma cells. In conclusion, our results indicated that miR-10a regulated cell proliferation and apoptosis by directly targeting MTMR3 and could function as a prognostic factor for progression of glioma.

Keywords: B-cell lymphoma 2; Wnt/β-catenin signaling; apoptosis; microRNA; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Carcinogenesis / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Protein Tyrosine Phosphatases, Non-Receptor / genetics*
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • Wnt Signaling Pathway*
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • MIRN10 microRNA, human
  • MicroRNAs
  • beta Catenin
  • MTMR3 protein, human
  • Protein Tyrosine Phosphatases, Non-Receptor