Abstract
BackgroundEmerging 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.MethodsBreast 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.ResultsIn 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.ConclusionsUpregulated miR-200a enhances treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer.
Highlights
Emerging evidence suggests molecular and phenotypic association between treatment resistance and epithelial–mesenchymal transition (EMT) in cancer
Exciting progress has been made with the chemotherapy of breast cancer, the development of chemoresistance remains a major obstacle to successful treatment of breast cancer [1]
Results miR-200a plays a role in chemoresistance of breast cancer cells In our previous studies, it has been shown that MDA-MB-231 and ZR-75-30 had low levels of miR200a
Summary
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 miR200a in EMT, the role of miR-200a in therapy resistance remains to be elucidated. Exciting progress has been made with the chemotherapy of breast cancer, the development of chemoresistance remains a major obstacle to successful treatment of breast cancer [1]. Accumulating evidence indicates that altered miRNA expression, such as miR-193a, miR-504 and miR-125b had been implicated in the response of tumor cells to chemotherapy and affected the sensitivity of cancer cells to treatment [2,3,4]. The molecular events of miR-200a linking EMT are becoming well defined, while the role of miR-200a in therapy resistance remains unclear
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