title: Genetic analysis and preliminary function study of miR-423 in breast cancer.
abstract: Common genetic variants (single nucleotide polymorphisms SNPs) in microRNA (miRNA) genes may alter their maturation or expression and play a role in the formation of human cancer. Recently, the association between the SNP rs6505162 in pre-miR-423 and cancer risk has been frequently evaluated in diverse populations and in a range of cancers. In this study, we determined the genotypes of SNP rs6505162 in 5 matched cell lines (breast cancer cell lines and their corresponding peripheral blood cell lines) and 114 matched clinical specimens (clinical breast carcinoma specimens and their corresponding normal tissues), compared the processing efficiency of pri-miRNA to mature forms between pre-miR-423-12C (wild-type) and pre-miR-423-12A (mutant-type) expression vectors, and evaluated the function of miR-423 on cell proliferation. Our data showed that two out of five breast cancer cell lines and 8.77 % (10/114) of tumors underwent somatic mutations of the rs6505162 SNP, and somatic mutation state was significantly correlated with the expression of clinicopathologic variables, proliferating cell nuclear antigen (PCNA) and mutant p53. The pre-miR-423-12C SNP blocked the endogenous processing of pri-miR-423 to its two mature miRNAs. Interestingly, selected pre-miR-423-12C stable cell population had lower proliferation ability than pre-miR-423-12A stable cell population. Moreover, miR-423 promoted cell proliferation in breast cancer cell lines through its miR-423-3p strand, not miR-423-5p. Taken together, these results suggest that the SNP rs6505162 in pre-miR-423 affects the mature miR expression, and miR-423 plays a potentially oncogenic role in breast tumorigenesis.
authors: State Key Laboratory of Medicinal Chemical Biology, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China.
authors: Huanhuan
authors: H
authors: Zhao
authors: Ang
authors: A
authors: Gao
authors: Zhiqian
authors: Z
authors: Zhang
authors: Ruoyu
authors: R
authors: Tian
authors: Ang
authors: A
authors: Luo
authors: Mei
authors: M
authors: Li
authors: Dan
authors: D
authors: Zhao
authors: Liya
authors: L
authors: Fu
authors: Li
authors: L
authors: Fu
authors: Jin-Tang
authors: JT
authors: Dong
authors: Zhengmao
authors: Z
authors: Zhu
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C548900:MIRN423 microRNA, human; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53