Z.G. and C.W. contributed equally to this work.
A polymorphism at the miR-502 binding site in the 3′-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome
Article first published online: 11 JAN 2012
Copyright © 2011 UICC
International Journal of Cancer
Volume 131, Issue 6, pages 1318–1322, 15 September 2012
How to Cite
Guo, Z., Wu, C., Wang, X., Wang, C., Zhang, R. and Shan, B. (2012), A polymorphism at the miR-502 binding site in the 3′-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome. Int. J. Cancer, 131: 1318–1322. doi: 10.1002/ijc.27352
- Issue published online: 20 JUL 2012
- Article first published online: 11 JAN 2012
- Accepted manuscript online: 18 NOV 2011 03:19AM EST
- Manuscript Accepted: 21 OCT 2011
- Manuscript Received: 2 AUG 2011
- National Natural Science Foundation of People's Republic of China. Grant Number: 30801384
- Natural Science Foundation of Hebei Province. Grant Number: C2008000958
MicroRNAs (miRNAs) can bind to the 3′-untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis and tumorigenesis. Genetic polymorphisms in the 3′-UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. The histone methyltransferase SET8 has been reported to methylate TP53 and regulate genomic stability. We analyzed a single-nucleotide polymorphism (rs16917496) within the miR-502 miRNA seed region for the 3′-UTR of SET8 in Chinese patients with hepatocellular carcinoma (HCC). The SET8 CC genotype was independently associated with longer postoperative survival in patients with HCC by multivariate analysis (relative risk, 0.175; 95% CI = 0.053–0.577; p = 0.004). The SET8 CC genotype was associated with reduced SET8 protein levels based on the immunostaining of 51 HCC tissue samples. We also found that the low SET8 levels were associated with longer HCC survival. Our data suggest that SET8 modifies HCC outcome by altering its expression, which depends, at least in part, on its binding affinity with miR-502. The analysis of genetic polymorphisms in miRNA binding sites can help to identify patient subgroups that are at high risk for poor disease outcomes.