A functional polymorphism inlnc-LAMC2-1:1confers 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.

Inhibition of Mir-128-3p by Tongxinluo Protects Human Cardiomyocytes From Ischemia/Reperfusion Injury via Upregulation of P70s6k1/P-P70s6k1

“…Another limitation is that we did not investigate how TXL downregulated miR-128-3p. Further research will be needed to elucidate whether TXL decreases miR-128-3p levels by directly inhibiting the transcription of its gene or, instead, acts in an indirect manner, such as by facilitating expression of endogenous RNAs (e.g., lnc-LAMC2-1:1 Gong et al, 2016) that compete with miR-128-3p.…”

Nighttime sleep duration and risk of nonalcoholic fatty liver disease: the Dongfeng-Tongji prospective study

“…NAFLD is a complex disease that is strongly influenced by numerous mechanisms including lifestyle management, gut microbial and metabolic factors (29). Besides, with the advances of recent genome-wide association studies (GWAS) and post-GWAS studies, genetic susceptibility is also established as important roles in the development of NAFLD (30)(31)(32)(33). Though evidence from previously experimental and epidemiologic studies reported links between short sleep duration and diabetes, obesity, and metabolic syndrome, conditions that are associated with increased NAFLD risk (11,34,35), we failed to provide evidence of short sleep duration with NAFLD.…”

Functional Polymorphisms of CTLA4 Associated with Aggressive Periodontitis in the Chinese Han Population

“…There is increasing evidence that SNPs located in the binding sites of miRNAs (miRSNPs) may cause a reduction or increase in the translation of the target mRNA by affecting the binding of a miRNA to its target genes, thus altering the susceptibility to disease [22,23]. Researchers have found that the rs2910164 polymorphism in the miR-146a precursor sequence may influence the susceptibility of the Chinese population to gastric cancer, while the SNPs rs4143815 and rs4819388 in the 3'UTRs of B7-H1 and B7-H2 genes are significantly related to the occurrence of gastric cancer [24,25].…”