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Genetic analysis and preliminary function study of miR-423 in breast cancer

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Tumor Biology

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.

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Acknowledgments

This work was supported by the National Nature Science Foundation of China (grant numbers: 81470118, 81272219, 31171250, and 30930038) and the Open Fund of State Key Laboratory of Medicinal Chemical Biology (Nankai University). 

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Author notes

  1. Huanhuan Zhao

    Present address: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China

Authors and Affiliations

  1. State Key Laboratory of Medicinal Chemical Biology, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin, China

    Huanhuan Zhao, Ang Gao, Zhiqian Zhang, Ruoyu Tian, Ang Luo, Mei Li, Dan Zhao, Liya Fu, Jin-Tang Dong & Zhengmao Zhu

  2. Key Laboratory of Breast Cancer Research, Department of Breast Cancer Pathology and Research Laboratory, Cancer Hospital of Tianjin Medical University, Tianjin, China

    Li Fu

  3. Department of Hematology and Medical Oncology, Emory Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA

    Jin-Tang Dong

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  1. Huanhuan Zhao
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  2. Ang Gao
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Correspondence to Zhengmao Zhu.

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Zhao, H., Gao, A., Zhang, Z. et al. Genetic analysis and preliminary function study of miR-423 in breast cancer. Tumor Biol. 36, 4763–4771 (2015). https://doi.org/10.1007/s13277-015-3126-7

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  • DOI: https://doi.org/10.1007/s13277-015-3126-7

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