Abstract 5222: microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma

Abstract

Abstract In this study, we uncovered microRNA-148a (miR-148a) as a novel prognostic and oncogenic microRNA in glioblastoma (GBM). MiR-148a expression was significantly higher in human GBM tissues, cell lines and stem cells (GSCs) as compared to normal human brain and astrocytes. High miR-148a levels were a risk indicator for GBM patient survival. MiR-148a increased GBM cell and GSC growth, survival, migration, and invasion as well as GSC neurosphere formation. We identified the EGFR regulator, MIG6, and the apoptosis regulator, BIM as two direct targets of miR-148a and showed with rescue experiments that they mediate the oncogenic effects of miR-148a. Importantly, by inhibiting MIG6 expression, miR-148a reduced EGFR trafficking to the Rab7-expressing late endosome/lysosomal compartments. This coincided with a reduction of EGFR degradation and induction of EGFR expression and activation. Lastly, inhibition of miR-148a expression led to a strong inhibition of GSC and GBM xenograft growth in vivo. These findings represent the first comprehensive analysis of the role of miR-148a in GBM. They show that miR-148a expression levels are predictive of patient survival and that this microRNA enhances malignancy by inhibiting apoptosis and indirectly activating EGFR. These results also suggest that miR-148a is a potential target for GBM therapy. Citation Format: Jungeun Kim, Ying Zhang, Michael Skalski, Josie Hayes, Benjamin Kefas, David Schiff, Benjamin Purow, Sarah Parsons, Sean Lawler, Roger Abounader. microRNA-148a is a prognostic oncomiR that targets MIG6 and BIM to regulate EGFR and apoptosis in glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5222. doi:10.1158/1538-7445.AM2014-5222