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

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.