期刊
BRITISH JOURNAL OF CANCER
卷 108, 期 5, 页码 1133-1142出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2013.56
关键词
renal cancer; miRNA; prognosis; HIF; VHL; hypoxia
类别
资金
- Cancer Research UK
- UCARE
- NIHR Oxford Biomedical Research Centre
- Wellcome Trust
- Royal College of Surgeons
- Oxford Health Services Research Committee
- Urological Foundation
- Urology Cancer Research and Education
- Higher Education Funding Council for England
- NIHR Oxford Comprehensive Biomedical Research Centre
- Cancer Research UK [16016] Funding Source: researchfish
Background: Clear cell renal cancer frequently harbours von Hippel-Lindau (VHL) gene mutations, leading to stabilisation of the hypoxia-inducible factors (HIFs) and expression of their target genes. We investigated HIF-1 and HIF-2 in the regulation of microRNA-210 (miR-210), and its clinical relevance in renal tumours. Methods: RCC4 and 786-O renal cancer cell lines transfected with either an empty vector or functional VHL and incubated in normoxia or hypoxia were examined for miR-210 expression. Hypoxia-inducible factor siRNAs were used to examine their regulation of miR-210. Seventy-one clear cell renal tumours were sequenced for VHL mutations. Expression of miR-210, VHL, CA9, ISCU and Ki-67 were determined by immunohistochemistry and qRT-PCR. Results: In addition to HIF-1 regulating miR-210 in renal cancer, HIF-2 can regulate this microRNA in the absence of HIF-1. MicroRNA-210 is upregulated in renal cancer compared with normal renal cortex tissue. MicroRNA-210 correlates negatively with its gene target ISCU at the protein and mRNA level. MicroRNA-210 correlated with positive outcome variables and negatively with Ki-67. Conclusion: We provide further evidence of miR-210 activity in vivo, and show that high miR-210 expression is associated with better clinico-pathological prognostic factors.
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