Identification of a hypoxia-regulated miRNA signature in bladder cancer and a role for miR-145 in hypoxia-dependent apoptosis

• DOI: 10.1038/bjc.2015.203
• Publication Date: 2015-07-21T20:01:17Z
• Authors: C Blick; A Ramachandran; R McCormick; S Wigfield; D Cranston; J Catto; A L Harris
• Keywords: Hypoxia; Hypoxia-Inducible Factors

Hypoxia leads to the stabilisation of hypoxia-inducible factor (HIF) transcription that drives expression target genes including microRNAs (miRNAs). MicroRNAs are known regulate many involved in tumourigenesis. The aim this study was identify hypoxia-regulated miRNAs (HRMs) bladder cancer and investigate their functional significance. Bladder cell lines were exposed normoxic hypoxic conditions interrogated for 384 by qPCR. Functional studies carried out using siRNA-mediated gene knockdown chromatin immunoprecipitations. Apoptosis quantified annexin V staining flow cytometry. HRM signature NMI includes miR-210, miR-193b, miR-145, miR-125-3p, miR-708 miR-517a. most hypoxia-upregulated miRNA miR-145. miR-145 a direct HIF-1α two hypoxia response elements identified within promoter region gene. Finally, upregulation contributed increased apoptosis RT4 cells. We have demonstrated regulation number cancer. shown is novel, robust HIF turn death lines.