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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2009-12-16
pubmed:abstractText
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)-1alpha (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-1alpha in vitro and in vivo. These findings suggest that functional polymorphism rs3783553 in IL1A could contribute to HCC susceptibility. Considering IL-1alpha 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-1alpha may be a promising target for immunotherapy, early diagnosis and intervention of HCC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1460-2180
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2064-9
pubmed:meshHeading
pubmed-meshheading:19917630-3' Untranslated Regions, pubmed-meshheading:19917630-Adult, pubmed-meshheading:19917630-Aged, pubmed-meshheading:19917630-Binding Sites, pubmed-meshheading:19917630-Carcinoma, Hepatocellular, pubmed-meshheading:19917630-Case-Control Studies, pubmed-meshheading:19917630-Female, pubmed-meshheading:19917630-Gene Deletion, pubmed-meshheading:19917630-Genotype, pubmed-meshheading:19917630-Humans, pubmed-meshheading:19917630-Interleukin-1alpha, pubmed-meshheading:19917630-Liver Neoplasms, pubmed-meshheading:19917630-Male, pubmed-meshheading:19917630-MicroRNAs, pubmed-meshheading:19917630-Middle Aged, pubmed-meshheading:19917630-Mutagenesis, Insertional, pubmed-meshheading:19917630-Polymorphism, Genetic, pubmed-meshheading:19917630-RNA Processing, Post-Transcriptional, pubmed-meshheading:19917630-Risk
pubmed:year
2009
pubmed:articleTitle
An insertion/deletion polymorphism at miRNA-122-binding site in the interleukin-1alpha 3' untranslated region confers risk for hepatocellular carcinoma.
pubmed:affiliation
Laboratory of Cellular and Molecular Tumor Immunology, Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Medical College, Soochow University, Suzhou 215123, Jiangsu, People's Repubic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't