MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer
Abstract Background Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial–mesenchymal transition (EMT) in cancer. Compared with the well-defined molecular events of miR-200a in EMT, the role of miR-200a in therapy resistance remains to be elucida...
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | BMC Cancer |
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| Online Access: | http://link.springer.com/article/10.1186/s12885-017-3930-0 |
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| author | San-Jian Yu Liu Yang Qi Hong Xia-Ying Kuang Gen-Hong Di Zhi-Ming Shao |
| author_facet | San-Jian Yu Liu Yang Qi Hong Xia-Ying Kuang Gen-Hong Di Zhi-Ming Shao |
| author_sort | San-Jian Yu |
| collection | DOAJ |
| description | Abstract Background Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial–mesenchymal transition (EMT) in cancer. Compared with the well-defined molecular events of miR-200a in EMT, the role of miR-200a in therapy resistance remains to be elucidated. Methods Breast cancer cells transfected with mimic or inhibitor for miR-200a was assayed for chemoresistance in vitro. miR-200a expression was assessed by quantitative real-time PCR (qRT-PCR) in breast cancer patients treated with preoperative chemotherapy. Luciferase assays, cell proliferation assay were performed to identify the targets of miR-200a and the mechanism by which it promotes treatment resistance. Survival analysis was used to evaluate the prognosis value of miR-200a. Results In this study, our results showed ectopic expression of miR-200a promotes chemoresistance in breast cancer cell lines to several chemotherapeutic agents, whereas inhibition of miR-200a enhances gemcitabine chemosensitivity in resistance cancer cells. We found overexpression of miR-200a was closely associated with poor response to preoperative chemotherapy and poor prognosis in breast cancer patients. Furthermore, knockdown of YAP1 and TP53INP1 phenocopied the effects of miR-200a overexpression, and confirmed that TP53INP1 is a novel target of miR-200a. Remarkably, TP53INP1 expression is inversely correlated with miR-200a expression in Breast cancer cell lines. Taken together, these clinical and experimental results demonstrate that miR-200a is a determinant of chemoresistance of breast cancer. Conclusions Upregulated miR-200a enhances treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer. |
| first_indexed | 2024-04-13T16:44:56Z |
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| id | doaj.art-c464380ae3b64753b35f13668fe448f2 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T16:44:56Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-c464380ae3b64753b35f13668fe448f22022-12-22T02:39:06ZengBMCBMC Cancer1471-24072018-01-0118111110.1186/s12885-017-3930-0MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancerSan-Jian Yu0Liu Yang1Qi Hong2Xia-Ying Kuang3Gen-Hong Di4Zhi-Ming Shao5Breast Cancer Institute, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan UniversityBreast Cancer Institute, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan UniversityBreast Cancer Institute, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan UniversityBreast Cancer Institute, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan UniversityBreast Cancer Institute, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan UniversityBreast Cancer Institute, Department of Breast Surgery, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Sciences, Fudan UniversityAbstract Background Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial–mesenchymal transition (EMT) in cancer. Compared with the well-defined molecular events of miR-200a in EMT, the role of miR-200a in therapy resistance remains to be elucidated. Methods Breast cancer cells transfected with mimic or inhibitor for miR-200a was assayed for chemoresistance in vitro. miR-200a expression was assessed by quantitative real-time PCR (qRT-PCR) in breast cancer patients treated with preoperative chemotherapy. Luciferase assays, cell proliferation assay were performed to identify the targets of miR-200a and the mechanism by which it promotes treatment resistance. Survival analysis was used to evaluate the prognosis value of miR-200a. Results In this study, our results showed ectopic expression of miR-200a promotes chemoresistance in breast cancer cell lines to several chemotherapeutic agents, whereas inhibition of miR-200a enhances gemcitabine chemosensitivity in resistance cancer cells. We found overexpression of miR-200a was closely associated with poor response to preoperative chemotherapy and poor prognosis in breast cancer patients. Furthermore, knockdown of YAP1 and TP53INP1 phenocopied the effects of miR-200a overexpression, and confirmed that TP53INP1 is a novel target of miR-200a. Remarkably, TP53INP1 expression is inversely correlated with miR-200a expression in Breast cancer cell lines. Taken together, these clinical and experimental results demonstrate that miR-200a is a determinant of chemoresistance of breast cancer. Conclusions Upregulated miR-200a enhances treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer.http://link.springer.com/article/10.1186/s12885-017-3930-0microRNABreast cancerChemoresistancePreoperative chemotherapy |
| spellingShingle | San-Jian Yu Liu Yang Qi Hong Xia-Ying Kuang Gen-Hong Di Zhi-Ming Shao MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer BMC Cancer microRNA Breast cancer Chemoresistance Preoperative chemotherapy |
| title | MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer |
| title_full | MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer |
| title_fullStr | MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer |
| title_full_unstemmed | MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer |
| title_short | MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer |
| title_sort | microrna 200a confers chemoresistance by antagonizing tp53inp1 and yap1 in human breast cancer |
| topic | microRNA Breast cancer Chemoresistance Preoperative chemotherapy |
| url | http://link.springer.com/article/10.1186/s12885-017-3930-0 |
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