Genomic analyses reveal miR-137 broad impact on genes associated with malignant transformation and neuronal differentiation in glioblastoma cells

miR-137 plays critical roles in the nervous system and tumor development. An increase in its expression is required for neuronal differentiation while its reduction is implicated in gliomagenesis. To evaluate the potential of miR-137 in glioblastoma therapy, we conducted genome-wide target mapping in glioblastoma cells by measuring levels of associations between PABP and mRNAs in cells transfected with miR-137 mimics vs. controls via RIPSeq. Impact on mRNA levels was also measured by RNASeq. By combining the results of both experimental approaches, 1468 genes were determined to be negatively impacted by miR-137; among them, 595 (40%) contain miR-137 predicted sites. The most relevant targets include oncogenic proteins and players in neurogenesis like c-KIT, YBX1, AKT2, CDC42, CDK6 and TGFβ2. Interestingly, we observed that several identified miR-137 targets are also predicted to be regulated by miR-124, miR-128 and miR-7, which are equally implicated in neuronal differentiation and gliomagenesis. We suggest that the concomitant increase of these four miRNAs in neuronal stem cells or their repression in tumor cells could produce a robust regulatory effect with major consequences to neuronal differentiation and tumorigenesis. Identification of genes affected by miR137 transfection via RIP-Seq and RNA-Seq in U251 and U343 cells