miR-145-5p is associated with pathological complete response to neoadjuvant chemotherapy and impairs cell proliferation by targeting TGF beta R2 in breast cancer
Por:
Garcia-Garcia, Frederik, Salinas-Vera, Yarely M., Garcia-Vazquez, Raul, Marchat, Laurence A., Rodriguez-Cuevas, Sergio, Sullivan Lopez-Gonzalez, Jose, Carlos-Reyes, Angeles, Ramos-Payan, Rosalio, Aguilar-Medina, Maribel, Perez-Plasencia, Carlos, Ruiz-Garcia, Erika, Lopez-Camarillo, Cesar
Publicada:
1 jun 2019
Resumen:
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 TGF beta R2 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 TGF beta R2.
Filiaciones:
Garcia-Garcia, Frederik:
Autonomous Univ Mexico City, Genom Sci Program, San Lorenzo 290, Mexico City 03100, DF, Mexico
Salinas-Vera, Yarely M.:
Autonomous Univ Mexico City, Genom Sci Program, San Lorenzo 290, Mexico City 03100, DF, Mexico
Garcia-Vazquez, Raul:
Inst Politecn Nacl, Mol Biomed Program, Mexico City 07320, DF, Mexico
Inst Politecn Nacl, Biotechnol Network, Mexico City 07320, DF, Mexico
Marchat, Laurence A.:
Inst Politecn Nacl, Mol Biomed Program, Mexico City 07320, DF, Mexico
Inst Politecn Nacl, Biotechnol Network, Mexico City 07320, DF, Mexico
Rodriguez-Cuevas, Sergio:
FUCAM, Breast Dis Inst, Mexico City 04980, DF, Mexico
Sullivan Lopez-Gonzalez, Jose:
Natl Inst Resp Dis Ismael Cosio Villegas, Lung Canc Lab, Mexico City 14080, DF, Mexico
Carlos-Reyes, Angeles:
Natl Inst Resp Dis Ismael Cosio Villegas, Lung Canc Lab, Mexico City 14080, DF, Mexico
Ramos-Payan, Rosalio:
Autonomous Univ Sinaloa, Fac Sci Chem Biol, Culiacan 80040, Sinaloa, Mexico
Aguilar-Medina, Maribel:
Autonomous Univ Sinaloa, Fac Sci Chem Biol, Culiacan 80040, Sinaloa, Mexico
Perez-Plasencia, Carlos:
Natl Inst Cancerol, Genom Lab, Mexico City 14080, DF, Mexico
Ruiz-Garcia, Erika:
Natl Inst Canc, Translac Med Lab, Mexico City 14080, DF, Mexico
Lopez-Camarillo, Cesar:
Autonomous Univ Mexico City, Genom Sci Program, San Lorenzo 290, Mexico City 03100, DF, Mexico
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