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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2016 Jan 15

PMID 26766590

Citations 62

Authors

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

Affiliations

Soon will be listed here.

Abstract

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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