Consistently, BDNF silencing had the same effects as miR-210 overexpression in glioblastoma, and upregulation of BDNF counteracted the inhibitory effect of miR-210 in glioblastoma.
Overall, our study identifies a novel role of NeuroD2 as a tumor suppressor and prognostic biomarker in GBM the levels of which are tightly regulated by p53 and miR-210.
Based on deep sequencing and microarray data, we identify a set of hypoxia regulated microRNAs, with the miR-210-3p and its isomiRs showing highest induction in GBM cell lines U87MG and U251MG.
Moreover, in the GBM dataset miR-21 and miR-210 were predictors of worse prognosis in both univariable and multivariable Cox regression analyses (HR 1.19, p = 0.04, and HR 1.18, p = 0.029 respectively).
Our results demonstrates that miR-326, miR-130a, miR-155, miR-210 and the 4 miRNA-interactions could serve as prognostic and predictive markers for survival of GBM patients, suggesting a potential application in improvement of prognostic tools and treatments.