Open AccessEvaluation of polymorphisms in microRNA‐binding sites and pancreatic cancer risk in Chinese population
Author(s) -
Ke Juntao,
Peng Xiating,
Mei Shufang,
Tian Jianbo,
Ying Pingting,
Yang Nan,
Wang Xiaoyang,
Zou Danyi,
Yang Yang,
Zhu Ying,
Gong Yajie,
Gong Jing,
Zhong Rong,
Chang Jiang,
Fang Zemin,
Miao Xiaoping
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14906
Subject(s) - microrna , single nucleotide polymorphism , biology , expression quantitative trait loci , odds ratio , genetics , snp , dna binding site , carcinogenesis , pancreatic cancer , population , bioinformatics , gene , cancer , gene expression , medicine , genotype , promoter , environmental health
As promising biomarkers and therapy targets, microRNAs (miRNAs) are involved in various physiological and tumorigenic processes. Genetic variants in miRNA‐binding sites can lead to dysfunction of miRNAs and contribute to disease. However, systematic investigation of the miRNA‐related single nucleotide polymorphisms (SNPs) for pancreatic cancer (PC) risk remains elusive. We performed integrative bioinformatics analyses to select 31 SNPs located in miRNA‐target binding sites using the miRNASNP v2.0, a solid database providing miRNA‐related SNPs for genetic research, and investigated their associations with risk of PC in two large case‐control studies totally including 1847 cases and 5713 controls. We observed that the SNP rs3802266 is significantly associated with increased risk of PC (odds ratio (OR) = 1.21, 95% confidence intervals (CI) = 1.11‐1.31, P = 1.29E‐05). Following luciferase reporter gene assays show that rs3802266‐G creates a stronger binding site for miR‐181a‐2‐3p in 3′ untranslated region (3′UTR) of the gene ZHX2 . Expression quantitative trait loci (eQTL) analysis suggests that ZHX2 expression is lower in individuals carrying rs3802266‐G with increased PC risk. In conclusion, our findings highlight the involvement of miRNA‐binding SNPs in PC susceptibility and provide new clues for PC carcinogenesis.