Abstract 3536: Roles of miR-215 and regulatory mechanisms for its biogenesis in response to hypoxia in glioblastoma stem cells

Abstract

Abstract Glioblastoma (GBM) is the most common and aggressive primary brain tumor in adults, which is highly resistant to conventional therapies. In GBM, glioblastoma stem cells (GSCs) are critical for the tumor progression and resistance. The hypoxic tumor microenvironment has been reported to help maintain GSCs. However, the mechanism regulating responses of GSCs to hypoxia remains elusive. Abnormal microRNA processing is a contributing factor in various types of cancer including GBM. Using small RNA deep sequencing and Real-time PCR array, we found a group of miRNAs altered in the expression levels under hypoxia in the CD133+ GSCs. Further through a functional screen, we identified miR-215 as an important mediator for GSC growth and tumor progression in response to hypoxia. In addition, we also investigated the regulatory mechanisms for the biogenesis of the altered miRNAs under hypoxia. Interestingly, we found that hypoxia could regulate miRNA processing both transcriptionally and post-transcriptionally. These findings suggest that de-regulated miRNA biogenesis may have significant impacts on the activities of GSCs under hypoxia. Citation Format: Jing Hu, Tao Sun, Hui Wang, Pingping Wang, Xiang-Dong Fu, Qi-Jing Li, Xiao-Fan Wang. Roles of miR-215 and regulatory mechanisms for its biogenesis in response to hypoxia in glioblastoma stem cells. [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 3536. doi:10.1158/1538-7445.AM2014-3536