%0 Journal Article
%T The VHL-dependent regulation of microRNAs in renal cancer
%A Calida S Neal
%A Michael Z Michael
%A Lesley H Rawlings
%A Mark B Van der Hoek
%A Jonathan M Gleadle
%J BMC Medicine
%D 2010
%I BioMed Central
%R 10.1186/1741-7015-8-64
%X VHL-dependent miRNA expression in cc RCC was determined by microarray analysis of renal cell line RCC4 with mutated VHL (RCC4-VHL) and reintroduced wild-type VHL (RCC4 + VHL). Five miRNAs highly upregulated in RCC4 + VHL and five miRNAs highly downregulated in RCC4 + VHL were studied further, in addition to miR-210, which is regulated by the HIF-VHL system. miRNA expression was also measured in 31 cc RCC tumours compared to adjacent normal tissue.A significant increase in miR-210, miR-155 and miR-21 expression was observed in the tumour tissue. miR-210 levels also showed a correlation with a HIF-regulated mRNA, carbonic anhydrase IX (CAIX), and with VHL mutation or promoter methylation. An inverse correlation was observed between miR-210 expression and patient survival, and a putative target of miR-210, iron-sulfur cluster assembly protein (ISCU1/2), shows reciprocal levels of mRNA expression in the tumours.We have identified VHL-regulated miRNAs and found that for some the regulation is HIF-dependent and for others it is HIF-independent. This pattern of regulation was also seen in renal cancer tissue for several of these miRNAs (miR-210, miR-155, let-7i and members of the miR-17-92 cluster) when compared with normal tissue. miR-210 showed marked increases in expression in renal cancer and levels correlated with patient survival. The inverse correlation between miR-210 levels and ISCU1/2 provides support for the hypothesis that ISCU1/2 is a target of miR-210 and that it may contribute to the anaerobic respiration seen in renal (and other) tumours.See Commentary: http://www.biomedcentral.com/1741-7015/8/65 webciteRenal cell carcinoma accounts for 2-3% of malignant diseases in adults, with an increasing worldwide incidence of over 200,000 new cases and 100,000 deaths per year [1]. The understanding of the pathogenesis of the commonest histological type, clear cell renal cell carcinoma (cc RCC), has been considerably advanced by the recognition that the gene encoding t
%U http://www.biomedcentral.com/1741-7015/8/64