miR-219a-5p inhibits breast cancer cell migration and epithelial-mesenchymal transition by targeting myocardin-related transcription factor A

Chunyu Zhuang, Ying Yuan, Tiefeng Song, Huiqin Wang, Liwen Huang, Xuegang Luo, Hongpeng He, Lihong Huo, Hao Zhou, Nan Wang, and Tongcun Zhang

Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China

Acta Biochim Biophys Sin 2017, 49: 1112–1121; doi: 10.1093/abbs/gmx114

Although many miRNAs are reported to be involved in tumor formation and progression, the effect of miR-219a-5p on breast cancer metastasis is not well-known. The aim of this study is to investigate the effect of miR-219a-5p on the migratory ability and epithelial-mesenchymal transition (EMT) of breast cancer cells. First, miR-219a-5p was found to be highly expressed in low-invasive breast cancer MCF-7 cells, but lowly expressed in high-invasive breast cancer MDA-MB-231 cells. Wound scratch assay and transwell assay showed that miR-219a-5p inhibited the migratory ability of MDA-MB-231 cells. miR-219a-5p also suppressed the cellular EMT, confirmed by suppressing the expression of mesenchymal markers vimentin and N-cadherin and increasing the expression of epithelial marker E-cadherin. Using the epithelial-mesenchymal-epithelial model in MCF-7 cells, we confirmed that the level of miR-219a-5p was highly expressed in epithelial-type cells and lowly expressed in mesenchymal-type cells. Importantly, we identified myocardin-related transcription factor A (MRTF-A) as a novel potential target gene of miR-219a-5p. Overexpression of miR-219a-5p in MDA-MB-231 cells could inhibit the expression of MRTF-A as revealed by real-time PCR and western blot analysis. miR-219a-5p inhibited the transcription of MRTF-A by targeting the 3′UTR of MRTF-A, which was confirmed by wild-type or mutant MRTF-A 3′UTR luciferase reporter system. Furthermore, knockdown of MRTF-A using siRNA for MRTF-A could depress breast cell migration. In conclusion, our present study revealed the tumor suppressive role of miR-219a-5p in regulating breast cancer migration by targeting MRTF-A, suggesting that miR-219a-5p might be a therapeutic target in breast cancer through regulating EMT.

miR-219a-5p inhibits breast cancer cell migration and EMT by targeting MRTF-A

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