MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B

Publication date: 11 January 2016
Source:Cancer Cell, Volume 29, Issue 1
Author(s): Jing Hu, Tao Sun, Hui Wang, Zhengxin Chen, Shuai Wang, Lifeng Yuan, Tingyu Liu, Hai-Ri Li, Pingping Wang, Yukuan Feng, Qinhong Wang, Roger E. McLendon, Allan H. Friedman, Stephen T. Keir, Darell D. Bigner, Jeff Rathmell, Xiang-dong Fu, Qi-Jing Li, Huibo Wang, Xiao-Fan Wang
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.

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Teaser

Hu et al. reveal an HIF-miR-215-KDM1B-mediated signaling axis in adaptation of glioma-initiating cells to hypoxia, and uncover a role of HIF in post-transcriptional regulation of miRNA biogenesis through HIF-Drosha interaction. MiR-215 level in GBM correlates with HIF1α level and tumor progression in patients.


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