miR‑145‑5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFβR2 in breast cancer

García‑García,Frederik; Salinas‑Vera,Yarely   M.; García‑Vázquez,Raúl; Marchat,Laurence   A.; Rodríguez‑Cuevas,Sergio; López‑González,José   Sullivan; Carlos‑Reyes,Ángeles; Ramos‑Payán,Rosalío; Aguilar‑Medina,Maribel; Pérez‑Plasencia,Carlos; Ruíz‑García,Erika; López‑Camarillo,César

doi:10.3892/or.2019.7102

miR‑145‑5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFβR2 in breast cancer

Authors:
- Frederik García‑García
- Yarely M. Salinas‑Vera
- Raúl García‑Vázquez
- Laurence A. Marchat
- Sergio Rodríguez‑Cuevas
- José Sullivan López‑González
- Ángeles Carlos‑Reyes
- Rosalío Ramos‑Payán
- Maribel Aguilar‑Medina
- Carlos Pérez‑Plasencia
- Erika Ruíz‑García
- César López‑Camarillo
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Affiliations: Genomics Sciences Program, Autonomous University of Mexico City, Mexico City 03100, Mexico, Molecular Biomedicine Program and Biotechnology Network, Instituto Politécnico Nacional, Mexico City 07320, Mexico, Breast Diseases Institute, FUCAM, Mexico City 04980, Mexico, Lung Cancer Laboratory, National Institute of Respiratory Diseases ‘Ismael Cosio Villegas’, Mexico City 14080, Mexico, Faculty of Sciences Chemistry Biologicals, Autonomous University of Sinaloa, Culiacán Sinaloa 80040, Mexico, Genomics Laboratory, National Institute of Cancerology, Mexico City 14080, Mexico, Translacional Medicine Laboratory, National Institute of Cancer, Mexico City 14080, Mexico
Published online on: April 5, 2019 https://doi.org/10.3892/or.2019.7102
Pages: 3527-3534

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Abstract

Cancer patients who better benefit from neoadjuvant chemotherapy (NeoCh) are those who achieve a successful pathological complete response (pCR) represented by the absence of residual disease. Unfortunately, no highly sensitive and specific tumor biomarkers for predicting the clinical response to NeoCh have yet been defined. The aim of the present study was to ascertain whether miR‑145‑5p could discriminate between pCR and no‑pCR in triple‑negative breast cancer patients that received a cisplatin/doxorubicin‑based neoadjuvant treatment. miR‑145‑5p expression was determined in breast tumors by quantitative RT‑PCR. Our data showed that miR‑145‑5p had a significant low expression (P<0.005) in patients that achieved pCR in comparison to the non‑responder group. Kaplan Meier analysis indicated that low levels of miR‑145‑5p were associated with increased disease‑free survival. In addition, receiver operating characteristic (ROC) curve analysis suggested that miR‑145‑5p is a good predictor of pCR (P<0.003, AUC=0.7899, 95% CI, 0.6382‑0.9416). Quantitative RT‑PCR expression analysis also revealed that miR‑145‑5p was downregulated in four breast cancer cell lines relative to normal cells. To study the functions of miR‑145‑5p, its expression was restored in triple‑negative MDA‑MB‑231 cells and its effects in cell proliferation were evaluated by MTT assays and in apoptosis using Annexin V experiments. Data revealed that ectopic expression of miR‑145‑5p resulted in a significant inhibition of cell proliferation and also induced apoptosis. Moreover, miR‑145‑5p led to sensitization of breast cancer cells to cisplatin therapy. In addition, western blot assays indicated that miR‑145‑5p downregulated the TGFβR2 protein. In conclusion, miR‑145‑5p could be a potential biomarker of clinical response to NeoCh in triple‑negative breast cancer. Functionally miR‑145‑5p may regulate cell proliferation, at least in part, by targeting TGFβR2.

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