Genetic variation at the microRNA binding site of CAV1 gene is associated with lung cancer susceptibility
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Xue Fang1,2,4, Xuelian Li1,2, Zhihua Yin1,2, Lingzi Xia1,2, Xiaowei Quan1,2, Yuxia Zhao3 and Baosen Zhou1,2
1Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China
2Liaoning Provincial Department of Education, Key Laboratory of Cancer Etiology and Prevention, China Medical University, Liaoning, China
3Department of Radiotherapy, The Fourth Affiliated Hospital of China Medical University, Shenyang, China
4Department of Epidemiology, School of Public Health, Shenyang Medical College, Shenyang, China
Baosen Zhou, email: [email protected]
Keywords: single nucleotide polymorphism, lung cancer, CAV1, microRNA
Received: April 27, 2017 Accepted: September 05, 2017 Published: October 09, 2017
Single nucleotide polymorphism (SNP) may influence the genesis and development of cancer in a variety of ways depending on their location. Here we conducted a study in Chinese female non-smokers to investigate the relationship between rs1049337, rs926198 and the risk or survival of lung cancer. Further, we explored whether rs1049337 could alter the binding affinity between the mRNA of CAV1 and the corresponding microRNAs. Finally, we evaluated the relationship between expression level of CAV1 and prognosis of lung cancer. The results showed that the rs1049337-C allele and rs926198-C allele were the protective alleles of lung cancer risk. Haplotype analysis indicated that the C-C haplotype (constructed by rs1049337 and rs926198) was a protective haplotype for lung cancer risk. The result of luciferase reporter assay showed that rs1049337 can affect the binding affinity of CAV1 mRNA to the corresponding microRNAs both in A549 cell line and H1299 cell line. Compared with C allele, T allele had a relatively decreased luciferase activity. Compared with paired normal adjacent tissue or normal lung tissue, lung cancer tissue showed a relatively low level of CAV1. Refer to those patients at early stage of lung cancer, the expression level of CAV1 in patients at late stage of lung cancer was relatively low. In conclusion, the results indicated that rs1049337, it’s a SNP located at 3’UTR region of CAV1 may affect lung cancer risk by altering the binding affinity between the mRNA of CAV1 and the corresponding microRNAs.
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