title: Somatic Mutation of the SNP rs11614913 and Its Association with Increased MIR 196A2 Expression in Breast Cancer.
abstract: Common genetic variants (single-nucleotide polymorphisms [SNPs]) in microRNA genes may alter their maturation or expression, resulting in varied functional consequences. Several studies have evaluated the association between the SNP rs11614913 and cancer risk in diverse populations and in a range of cancers, with contradictory outcomes. In this study, we examined 114 paired samples (tumor and normal tissues) from breast cancer patients to study the genotype distribution and somatic mutation of the SNP in MIR 196A2 (rs11614913 C-T). In addition, we evaluated their influence on the mature MIR 196A2 expression. We found that 14% (16/114) of tumors underwent somatic mutation of the SNP rs11614913. Moreover, the CT heterozygous and the CC homozygous states of SNP rs11614913 were more prone to mutation, while the TT homozygous state appeared to be resistant. We further detected a significant increase (p = 0.002) in mature MIR 196A2 expression in breast cancer. In particular, we found a significant association between the occurrence of SNP rs11614913 mutation and high expression (p = 0.0002). In addition, the mature MIR 196A2 expression level was significantly associated with the higher tumor grade (p = 0.004). Taken together, our results seem to demonstrate that somatic mutation of SNP rs11614913 in MIR 196A2 can have an influence on its expression. In addition, it indicated that an unknown mechanism is responsible for both the mutation of SNP rs11614913 and the dysregulation of mature MIR 196A2 expression.
authors.affiliation: 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, China .|2 State Key Laboratory of Medicinal Chemical Biology, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Huanhuan
authors.initials: H
authors.lastname: Zhao
authors.affiliation: 3 Medical Experimental Research Center, North China University of Science and Technology , Tangshan, China .
authors.forename: Jingman
authors.initials: J
authors.lastname: Xu
authors.affiliation: 2 State Key Laboratory of Medicinal Chemical Biology, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.affiliation: 4 Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University , Tianjin, China .
authors.forename: Meijuan
authors.initials: M
authors.lastname: Geng
authors.affiliation: 5 Clinical Laboratory of Tianjin Third Central Hospital , Tianjin, China .
authors.forename: Haize
authors.initials: H
authors.lastname: Ge
authors.affiliation: 6 Key Laboratory of Breast Cancer Research, Department of Breast Cancer Pathology and Research Laboratory, Cancer Hospital of Tianjin Medical University , Tianjin, China .
authors.forename: Li
authors.initials: L
authors.lastname: Fu
authors.affiliation: 2 State Key Laboratory of Medicinal Chemical Biology, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University , Tianjin, China .
authors.forename: Zhengmao
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide
chemical_list: C542543:MIRN196 microRNA, human; D035683:MicroRNAs