MiR-519a functions as a tumor suppressor in glioma by targeting the oncogenic STAT3 pathway

J Neurooncol. 2016 May;128(1):35-45. doi: 10.1007/s11060-016-2095-z. Epub 2016 Mar 12.

Abstract

Glioblastoma (GBM) is among the most aggressive primary brain tumors, with a median survival rate of 12-15 months. MicroRNAs have been implicated in GBM development as oncogenes or tumor suppressors. In this study, we demonstrated that miR-519a expression was frequently downregulated in GBM specimens and cell lines, and that low-levels miR-519a expression significantly correlated with poor outcomes associated with GBM. Analysis of The Cancer Genome Atlas also demonstrated that low miR-519a expression can predict poor clinical outcomes in classical and proneural GBM subtypes. Functionally, re-expression of miR-519a effectively reduced GBM cell proliferation, migration, and invasion. Mechanistically, we confirmed that the signal transducer and activator of transcription 3 (STAT3) 3'-UTR was a putative target of miR-519a, and that re-expression of STAT3 abrogated miR-519a function in GBM cells. Furthermore, we found that STAT3 expression negatively correlated with that of miR-519a in human GBM tissues. These results elucidated the prognostic value and tumor-suppressor role of miR-519a in GBM and further suggested it as a potential therapeutic target for GBM treatment.

Keywords: C19MC; Glioblastoma; STAT3; miR-519a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Brain / metabolism
  • Brain / pathology
  • Brain / surgery
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Cell Cycle / physiology
  • Cell Line
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Cohort Studies
  • Disease Progression
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Glioblastoma / surgery
  • Humans
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / physiopathology
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • Survival Analysis
  • Transcription, Genetic

Substances

  • MIRN519 microRNA, human
  • MicroRNAs
  • STAT3 Transcription Factor
  • STAT3 protein, human