MicroRNA-200a confers chemoresistance by antagonizing TP53INP1 and YAP1 in human breast cancer

BMC Cancer. 2018 Jan 12;18(1):74. doi: 10.1186/s12885-017-3930-0.

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.

Keywords: Breast cancer; Chemoresistance; Preoperative chemotherapy; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Carrier Proteins / genetics*
  • Cell Cycle Proteins
  • Cell Proliferation / genetics
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Drug Resistance, Neoplasm / genetics
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Heat-Shock Proteins / genetics*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / genetics*
  • Nuclear Proteins / genetics*
  • Prognosis
  • Transcription Factors / genetics*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Heat-Shock Proteins
  • MIRN200 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • TP53INP1 protein, human
  • Transcription Factors
  • YY1AP1 protein, human
  • Deoxycytidine
  • gemcitabine