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
  • View Affiliations

  • 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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June 2019
Volume 41 Issue 6

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APA
García‑García, F., Salinas‑Vera, Y.M., García‑Vázquez, R., Marchat, L.A., Rodríguez‑Cuevas, S., López‑González, J.S. ... López‑Camarillo, C. (2019). miR‑145‑5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFβR2 in breast cancer. Oncology Reports, 41, 3527-3534. https://doi.org/10.3892/or.2019.7102
MLA
García‑García, F., Salinas‑Vera, Y. M., García‑Vázquez, R., Marchat, L. A., Rodríguez‑Cuevas, S., López‑González, J. S., Carlos‑Reyes, Á., Ramos‑Payán, R., Aguilar‑Medina, M., Pérez‑Plasencia, C., Ruíz‑García, E., López‑Camarillo, C."miR‑145‑5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFβR2 in breast cancer". Oncology Reports 41.6 (2019): 3527-3534.
Chicago
García‑García, F., Salinas‑Vera, Y. M., García‑Vázquez, R., Marchat, L. A., Rodríguez‑Cuevas, S., López‑González, J. S., Carlos‑Reyes, Á., Ramos‑Payán, R., Aguilar‑Medina, M., Pérez‑Plasencia, C., Ruíz‑García, E., López‑Camarillo, C."miR‑145‑5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFβR2 in breast cancer". Oncology Reports 41, no. 6 (2019): 3527-3534. https://doi.org/10.3892/or.2019.7102