title: Association between indel polymorphism in the promoter region of lncRNA GAS5 and the risk of hepatocellular carcinoma.
abstract: The growth arrest special 5 (GAS5) is known to be involved in various cancers. However, its expression regulation remains unclear. Polymorphisms in the promoter region of GAS5 may affect its expression and be associated with cancer susceptibility. In this research, we first evaluated the association of a 5-base pair indel polymorphism (rs145204276) in the promoter region of GAS5 with hepatocelluar carcinoma (HCC) susceptibility in Chinese populations. Logistic regression analysis showed that the deletion allele of rs145204276 significantly increased the risk of HCC in two independent case control sets (1034 HCC and 1054 controls). Further genotype-phenotype association analysis revealed that the deletion allele was markedly correlated with higher expression of GAS5 in HCC tissues. The luciferase activity analysis in an in vitro reporter gene system suggested that the deletion allele improved an increased expression of GAS5 in three hepatoma cell lines. Intriguingly, overexpression of GAS5 displayed an anti-apoptosis effect in HCC cell lines, GAS5 knockdown could partially revert this anti-apoptosis effect, suggesting that GAS5 may act as a proto-oncogene in HCC, in contrast with its inhibitory role in other cancers. Further pyrosequencing revealed that the genotypes of rs145204276 were associated with methylation status of GAS5 promoter region. Taken together, our findings provided evidence that rs145204276 may contribute to hepatocarcinogenesis by affecting methylation status of the GAS5 promoter and subsequently its transcriptional activity thus serving as a potential therapy target for HCC.
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Ruiyang
authors.initials: R
authors.lastname: Tao
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Shuxiang
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Shouyu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Laboratory of Neurological Diseases, Department of Neurology, Changzhou No.2 People's Hospital, The Affiliated Hospital of Nanjing Medical University, Changzhou 213003, Jiangsu, China.
authors.forename: Xianju
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Xiankun
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Sciences, Ministry of Justice, PR China, Shanghai 200063, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Forensic Medicine, Institute of Forensic Sciences, Ministry of Justice, PR China, Shanghai 200063, China.
authors.forename: Chengtao
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Epidemiology, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Medical Molecular Virology, MOE and MOH, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China and.
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, OH 45219, USA.
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Forensic Medicine, Medical College of Soochow University, Suzhou 215123, Jiangsu, China, yuzhengao@suda.edu.cn.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000328:Adult; D000483:Alleles; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D062085:RNA, Long Noncoding / Q000235:genetics*
chemical_list: C561567:GAS5 long non-coding RNA, human; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D062085:RNA, Long Noncoding