title: Polymorphism in mature microRNA-608 sequence is associated with an increased risk of nasopharyngeal carcinoma.
abstract: Accumulative evidences indicated that microRNAs (miRNAs) can function as tumor suppressors and oncogenes, in which genetic variations are implicated in various cancer susceptibilities. However, it remains unclear whether single nucleotide polymorphisms (SNPs) in mature miRNA sequence alter nasopharyngeal carcinoma (NPC) susceptibility. In this study, we analyzed associations between eight SNPs in miRNA mature sequences (i.e., rs3746444T>C in hsa-mir-499, rs4919510C>G in hsa-mir-608, rs13299349G>A in hsa-mir-3152, rs12220909G>C in hsa-mir-4293, rs2168518G>A in hsa-mir-4513, rs8078913T>C in hsa-mir-4520a, rs11237828T>C in hsa-mir-5579, and rs9295535T>C in hsa-mir-5689) and NPC susceptibility in southern China with 906 NPC cases and 1072 cancer-free controls, and validated the significant findings in eastern China with 684 cases and 907 healthy controls. Functional assays were further performed to identify the biological effects of these polymorphisms. We found that rs4919510C>G polymorphism showed a consistent association with NPC risk in southern China (GC+GG versus CC genotype, odds ratio [OR]=1.36, 95% confidence interval [CI]=1.10-1.70) and eastern China (GC+GG versus CC: OR=1.37, 95% CI=1.08-1.74). After the two populations were merged, the ORs and 95% CI were 1.38 and 1.18 to 1.62, respectively. Moreover, the rs4919510C>G adverse genotypes significantly interacted with Epstein-Barr virus (EBV) infection on increasing NPC risk (P=0.001). The functional assay further showed that the CNE-2 cell lines that transfected with miR-608-rs4919510G allele expression vector exerted more colony number formations than cell lines that transfected with miR-608-rs4919510C allele expression vector (P=0.001). These data suggested that rs4919510C>G of miR-608 may be a susceptible biomarker of NPC in China.
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Fuman
authors: F
authors: Qiu
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Lei
authors: L
authors: Yang
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Lisha
authors: L
authors: Zhang
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Xiaorong
authors: X
authors: Yang
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Rongrong
authors: R
authors: Yang
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Wenxiang
authors: W
authors: Fang
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Di
authors: D
authors: Wu
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Jiansong
authors: J
authors: Chen
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Chenli
authors: C
authors: Xie
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China.
authors: Dongsheng
authors: D
authors: Huang
authors: Department of Genetics, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, PR China.
authors: Yifeng
authors: Y
authors: Zhou
authors: The State Key Lab of Respiratory Disease, The Institute for Chemical Carcinogenesis, Collaborative Innovation Center for Environmental Toxicity, Guangzhou Medical University, 195 Dongfengxi Road, Guangzhou 510182, PR China. Electronic address: jcLu@gzhmu.edu.cn.
authors: Jiachun
authors: J
authors: Lu
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D002277:Carcinoma; D016022:Case-Control Studies; D002460:Cell Line; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk
chemical_list: C000591804:MIRN608 microRNA, human; D035683:MicroRNAs
keywords: Epstein–Barr virus; Nasopharyngeal carcinoma; Polymorphism; Susceptibility; microRNA-608