An indel polymorphism in the 3' untranslated region of JAK1 confers risk for hepatocellular carcinoma possibly by regulating JAK1 transcriptional activity in a Chinese population.

The purpose of the present study was to assess whether the rs112395617 polymorphism located in the Janus kinase 1 (JAK1) 3' untranslated region (3' UTR) was associated with the risk of hepatocellular carcinoma (HCC), and to explore the potential mechanism of action. Genomic DNA was extracted from peripheral blood of 290 patients with HCC and 320 controls. A polymerase chain reaction-polyacrylamide gel electrophoresis assay was used to genotype the rs112395617 polymorphism. Quantitative (q)PCR was used to detect the genotype-phenotype association between HCC tissues and different genotypes. Vectors containing the insertion (ins)/ins or deletion (del)/del genotype of the rs112395617 polymorphism were constructed, and the luciferase assay was used to detect the JAK1 transcriptional activity affected by the rs112395617 polymorphism. It was identified that, when compared with the ins/ins genotype, the del/del and del/ins genotypes of rs112395617 were significantly associated with a decreased risk of HCC. The qPCR results demonstrated that the JAK1 mRNA expression level with ins/ins and ins/del genotypes was increased by 3.36 and 1.75-fold compared with the del/del genotype in human HCC tissue samples. In addition, the 'AATT' insertion allele of rs112395617 disrupted the binding site for microRNA (miR)-431-5p, thereby increasing JAK1 transcription in vitro. These data suggest that the rs112395617 polymorphism may contribute to HCC susceptibility, in full or at least partially through an effect on JAK1 transcriptional activity by disrupting its binding with miR-431-5p.