title: An indel polymorphism within pre-miR3131 confers risk for hepatocellular carcinoma.
abstract: Polymorphisms in pre-miRNAs may affect its expression, then have effect on its target mRNAs and be associated with cancer susceptibility. In this study, we evaluated the association of an indel polymorphism rs57408770 in pre-miR-3131 with hepatocellular carcinoma (HCC) susceptibility in a Chinese population. The contribution of rs57408770 to HCC risk was investigated in two independent case-control sets (1051 HCC and 1058 controls). Logistic regression analysis showed that the insertion allele of rs57408770 was significantly associated with an increased risk for HCC occurrence in both case-control studies. Moreover, the results of genotype-phenotype correlation analysis from both in vivo and in vitro experiments showed that the insertion allele was significantly correlated with higher expression of mature miR-3131 comparing with the deletion allele. The RNA-Binding Protein Immunoprecipitation assay results indicated that rs57408770 could affect the expression level of mature miR-3131 probably through disturbing the binding of splicing factor SRp20 with pre-miR-3131. Furthermore, overexpression of miR-3131 displayed a proliferation promoting and anti-apoptosis effect on HCC cell lines, suggesting that miR-3131 may act as a proto-oncogene in HCC. Finally, human genome-wide gene expression profile assay was used to screen the targets of miR-3131. The overexpressed miR-3131 could lead to a significant decrease of DTHD1 and XAF1 mRNA level. Taken together, our findings provided evidence that rs57408770 may play a functional role in the carcinogenesis of HCC by affecting SRp20 binding with pre-miR-3131 and affecting the expression of mature miR-3131, subsequently affecting the expression of DTHD1 and XAF1, thus confers risk for HCC.
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Zhixia
authors.initials: Z
authors.lastname: Yin
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, the First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, P.R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Ruiyang
authors.initials: R
authors.lastname: Tao
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Epidemiology, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Nuhigh Biotechnology, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Sciences, Ministry of Justice, Shanghai 200063, P.R. China.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Sciences, Ministry of Justice, Shanghai 200063, P.R. China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Medical Molecular Virology, MOE & MOH, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Neurobiology and Psychology, Key Laboratory of Pain Research & Therapy, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Xinghong
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, P.R. China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Gao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000368:Aged; D051017:Apoptosis Regulatory Proteins; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002681:China; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D012307:Risk Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C000622167:DTHD1 protein, human; D053418:Death Domain Receptor Signaling Adaptor Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000715470:MAS1 protein, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; C417551:XAF1 protein, human; C000622166:microRNA 3131, human