miR-219a-5p inhibits breast cancer cell migration and epithelial-mesenchymal transition by targeting myocardin-related transcription factor A
| Autor: | Ying Yuan, Tong-Cun Zhang, Huiqin Wang, Hao Zhou, Chun-Yu Zhuang, Nan Wang, Hongpeng He, Tie-Feng Song, Lihong Huo, Xue-Gang Luo, Liwen Huang |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition Biophysics Breast Neoplasms Vimentin Biochemistry 03 medical and health sciences Breast cancer Cell Movement microRNA medicine Humans Genes Tumor Suppressor Epithelial–mesenchymal transition Neoplasm Metastasis Transcription factor Gene knockdown biology Cell migration Hep G2 Cells General Medicine medicine.disease MicroRNAs 030104 developmental biology Myocardin MCF-7 Cells Trans-Activators biology.protein Cancer research Female |
| Zdroj: | Acta Biochimica et Biophysica Sinica. 49:1112-1121 |
| ISSN: | 1672-9145 |
| DOI: | 10.1093/abbs/gmx114 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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