The online version of this article (https://doi.org/10.1186/s12885-017-3930-0) contains supplementary material, which is available to authorized users.
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.
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.
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.
Upregulated miR-200a enhances treatment resistance via antagonizing TP53INP1 and YAP1 in breast cancer.
Additional file 1: Table S1. List of primer and siRNA sequences. Table S2: Intersection between predict target of miR-200a and p53 family binding partner. (DOCX 17 kb)12885_2017_3930_MOESM1_ESM.docx
Additional file 2: Fig. S1. Expression of p73 in MDA-MB-231 and MDA-MB-231 GR cells. (EPS 588 kb)12885_2017_3930_MOESM2_ESM.eps
SJ Y, JY H, Kuang XY, Luo JM, Hou YF, Di GH, Wu J, Shen ZZ, Song HY, Shao ZM. MicroRNA-200a promotes anoikis resistance and metastasis by targeting YAP1 in human breast cancer. Clin Cancer Res. 2013;19(6):1389–99. CrossRef
S-J Y, J-Y H, Kuang X-Y, Luo J-M, Hou Y-F, Di G-H, Wu J, Shen Z-Z, Song H-Y, Shao Z-M. MicroRNA-200a promotes Anoikis resistance and metastasis by targeting YAP1 in human breast cancer. Clin Cancer Res. 2013;19(6):1389–99. CrossRef
S-J Y, Yang L, Hong Q, Shao Z-M. Overexpression of miR-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human. breast cancer. 2005; https://www.sabcs.org/Portals/SABCS2016/Documents/SABCS-2015-Abstracts.pdf?v=5
- MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer
- BioMed Central
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