Journal Article

An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1α 3′ untranslated region confers risk for hepatocellular carcinoma

Yuzhen Gao, Yan He, Jun Ding, Kang Wu, Bo Hu, Yang Liu, Yan Wu, Bingnan Guo, Yueping Shen, Debora Landi, Stefano Landi, Yifeng Zhou and Haiyan Liu

in Carcinogenesis

Volume 30, issue 12, pages 2064-2069
Published in print December 2009 | ISSN: 0143-3334
Published online November 2009 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgp283
An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1α 3′ untranslated region confers risk for hepatocellular carcinoma

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Hepatocellular carcinoma (HCC) is the fifth most common malignancy caused by environmental and genetic factors. MicroRNAs (miRNAs) are a class of short non-coding RNAs with posttranscriptional regulatory functions. They participate in diverse biological pathways and function as gene regulators. Genetic polymorphisms in 3′ untranslated regions (3′ UTRs) targeted by miRNAs alter the strength of miRNA binding, with consequences on regulation of target genes thereby affecting the individual's cancer risk. We have previously predicted polymorphisms falling in miRNA-binding regions of cancer genes. We selected an insertion/deletion (Indel) polymorphism (rs3783553) in the 3′ UTR of interleukin (IL)-1α (IL1A) for a case–control study in a Chinese population. With samples from 403 HCC patients and 434 healthy control individuals, strong evidence of association was observed for the variant homozygote. This association was validated in a second independent case–control study with 1074 HCC patients and 1239 healthy control individuals (odds ratio = 0.62; 95% confidence interval = 0.49–0.78). We further show that the ‘TTCA’ insertion allele for rs3783553 disrupts a binding site for miR-122 and miR-378, thereby increasing transcription of IL-1α in vitro and in vivo. These findings suggest that functional polymorphism rs3783553 in IL1A could contribute to HCC susceptibility. Considering IL-1α affects not only various phases of the malignant process, such as carcinogenesis, tumor growth and invasiveness, but also patterns of interactions between malignant cells and the host's immune system, our results indicated that IL-1α may be a promising target for immunotherapy, early diagnosis and intervention of HCC.

Journal Article.  4203 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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