MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.
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The hypoxic tumor microenvironment serves as a niche for maintaining the glioma-initiating cells (GICs) that are critical for glioblastoma (GBM) occurrence and recurrence. Here, we report that hypoxia-induced miR-215 is vital for reprograming GICs to fit the hypoxic microenvironment via suppressing the expression of an epigenetic regulator KDM1B and modulating activities of multiple pathways. Interestingly, biogenesis of miR-215 and several miRNAs is accelerated post-transcriptionally by hypoxia-inducible factors (HIFs) through HIF-Drosha interaction. Moreover, miR-215 expression correlates inversely with KDM1B while correlating positively with HIF1α and GBM progression in patients. These findings reveal a direct role of HIF in regulating miRNA biogenesis and consequently activating the miR-215-KDM1B-mediated signaling required for GIC adaptation to hypoxia.
Cell Line, Tumor
Gene Expression Regulation, Neoplastic
Neoplasm Recurrence, Local
Published Version (Please cite this version)10.1016/j.ccell.2015.12.005
Publication InfoHu, Jing; Sun, Tao; Wang, Hui; Chen, Zhengxin; Wang, Shuai; Yuan, Lifeng; ... Wang, Xiao-Fan (2016). MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B. Cancer Cell, 29(1). pp. 49-60. 10.1016/j.ccell.2015.12.005. Retrieved from https://hdl.handle.net/10161/11667.
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