MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B.
Data(s) |
11/01/2016
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Formato |
49 - 60 |
Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/26766590 S1535-6108(15)00469-9 Cancer Cell, 2016, 29 (1), pp. 49 - 60 http://hdl.handle.net/10161/11667 1878-3686 |
Relação |
Cancer Cell 10.1016/j.ccell.2015.12.005 |
Tipo |
Journal Article |
Cobertura |
United States |
Resumo |
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. |
Idioma(s) |
ENG |
Palavras-Chave | #Animals #Brain Neoplasms #Cell Hypoxia #Cell Line, Tumor #Gene Expression Regulation, Neoplastic #Glioma #Humans #Mice, Nude #MicroRNAs #Neoplasm Recurrence, Local #Oxidoreductases, N-Demethylating #Tumor Microenvironment |