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

Abstract

The purpose of the present study was to assess whether the rs112395617 polymorphism located in the Janus kinase 1 () 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 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 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 transcription. These data suggest that the rs112395617 polymorphism may contribute to HCC susceptibility, in full or at least partially through an effect on transcriptional activity by disrupting its binding with miR-431-5p.

Dysregulation of miR‐431 and target gene FOXA1 in intestinal tissues of infants with necrotizing enterocolitis

“…Our previous study compared expressions of miRs in NEC, spontaneous intestinal perforation, and surg‐ctl bowel tissues and demonstrated significant up‐regulation of miR‐431 in NEC (7.05‐fold) and spontaneous intestinal perforation (4.15‐fold), suggesting possible involvement of miR‐413 in gut inflammation of these neonatal conditions (9). To date, very little has been reported on miR‐431 besides its involvement in the development of muscle (21, 22), neuronal conditions (23, 24), and pancreatic and hepatic malignancy (25, 26). Any potential influence of miR‐431 on adult gut inflammatory conditions such as Crohn's disease and ulcerative colitis has also not been described.…”

RNA regulatory mechanisms that control antiviral innate immunity

“…201 However, our laboratory has shown that while expression. 203 While intriguing, more precise functional dissection of these polymorphisms and their interplay with microRNAs is required for full understanding of their effect on antiviral immunity.…”

“…Of these isoforms, only p42 or p46 are expressed robustly at the protein level due to the instability of the other protein variants and of the RNA isoforms encoding them. [203][204][205] The expression of OAS1 p42 or p46 is controlled by the SNP rs10774671A/G in the splice acceptor site of exon 6. The G allele of this SNP shifts the splice acceptor site by one nucleotide and thus generates p46 with a novel C-terminal amino acid sequence that includes a terminal CaaX motif, subject to post-translational prenylation.…”

Association of KRAS Gene and microRNA-124-3p in Sporadic Colorectal Tumours

“…Somatic 3'UTR variants are more common in solid tumours compared to normal cells. However, it has been reported that variations defined in the 3'UTR regions of genes involved in the carcinogenesis process may be associated with low survival and poor prognosis [12].…”