TY - JOUR
T1 - MiR‑145‑5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGFβR2 in breast cancer
AU - García‑García, Frederik
AU - Salinas‑Vera, Yarely M.
AU - García‑Vázquez, Raúl
AU - Marchat, Laurence A.
AU - Rodríguez‑Cuevas, Sergio
AU - López‑González, José Sullivan
AU - Carlos‑Reyes, Ángeles
AU - Ramos‑Payán, Rosalío
AU - Aguilar‑Medina, Maribel
AU - Pérez‑Plasencia, Carlos
AU - Ruíz‑García, Erika
AU - López‑Camarillo, César
N1 - Publisher Copyright:
© 2019 Spandidos Publications. All rights reserved.
PY - 2019/6
Y1 - 2019/6
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Breast cancer
KW - Cell proliferation
KW - MiR‑145‑5p
KW - Neoadjuvant therapy
KW - Pathological complete response
KW - TGFβR2
UR - http://www.scopus.com/inward/record.url?scp=85064429416&partnerID=8YFLogxK
U2 - 10.3892/or.2019.7102
DO - 10.3892/or.2019.7102
M3 - Artículo
C2 - 31002371
SN - 1021-335X
VL - 41
SP - 3527
EP - 3534
JO - Oncology Reports
JF - Oncology Reports
IS - 6
ER -