title: A functional polymorphism in lnc-LAMC2-1:1 confers risk of colorectal cancer by affecting miRNA binding.
abstract: Genome-wide association studies (GWASs) have identified multiple susceptibility loci of colorectal cancer (CRC), however, causative polymorphisms have not been fully elucidated. Long non-coding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs that involved in a wide variety of biological processes. We hypothesized that single nucleotide polymorphisms (SNPs) in lncRNA may associate with the CRC risk by influencing lncRNA functions. To evaluate the effects of SNPs on CRC susceptibility in Chinese populations, we first screened out all potentially functional SNPs in exons of lncRNAs located in CRC susceptibility loci identified by GWAS. Eight SNPs were selected and genotyped in 875 CRC cases and 855 controls and replicated in an independent case-control study consisting of 768 CRC cases and 768 controls. Analyses showed that CG and GG genotypes of the rs2147578 were significantly associated with increased risk for CRC occurrence in both case-control studies [combined analysis OR = 1.29; 95% confidence interval (CI) = 1.11-1.51, P = 0.001] compared to the rs2147578 CC genotype. Bioinformatics analyses showed that rs2147578 is located in the transcript of lnc-LAMC2-1:1 and could influence the binding of lnc-LAMC2-1:1/miR-128-3p. Further luciferase reporter assays demonstrated that the construct with the risk rs2147578G allele had relatively high expression activity compared with that of the rs2147578C allele. Expression quantitative trait loci analyses also showed that rs2147578 is correlated with the expression of a well established oncogene LAMC2 (laminin subunit gamma 2). These findings indicated that rs2147578 in lnc-LAMC2-1:1 might be a genetic modifier for the development of CRC.
authors.forename: Jing
authors.initials: J
authors.lastname: Gong
authors.forename: Jianbo
authors.initials: J
authors.lastname: Tian
authors.forename: Jiao
authors.initials: J
authors.lastname: Lou
authors.forename: Juntao
authors.initials: J
authors.lastname: Ke
authors.affiliation: Research Center for Medicine and Biology, Zunyi Medical University, Zunyi, Guizhou, China and.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.forename: Jiaoyuan
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Yajie
authors.initials: Y
authors.lastname: Gong
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhong
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Chang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Miao
mesh_terms: D000368:Aged; D044466:Asian People; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007797:Laminin / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism
chemical_list: C400567:LAMC2 protein, human; D007797:Laminin; C545189:MIRN128 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding