A polymorphism at the miR-502 binding site in the 3′-untranslated region of the histone methyltransferase SET8 is associated with hepatocellular carcinoma outcome

Authors

  • Zhanjun Guo,

    1. Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
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    • Z.G. and C.W. contributed equally to this work.

  • Chensi Wu,

    1. Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
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    • Z.G. and C.W. contributed equally to this work.

  • Xiaoling Wang,

    1. Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
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  • Cuiju Wang,

    1. Department of Gynaecology Ultrasound, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
    2. Hebei Key Lab of Laboratory Animal Science, Hebei Medical University, Shijiazhuang, People's Republic of China
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  • Ruixing Zhang,

    1. Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
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  • Baoen Shan

    Corresponding author
    1. Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China
    • Research Center, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang 050011, People's Republic of China
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    • Tel: +86-311-86095283, Fax: +86-311-86992004


Abstract

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.

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