Tormo, EduardoBallester, SandraAdam-Artigues, AnnaBurgués, OctavioAlonso, ElisaBermejo, BegoñaMenendez Romero, SilviaZazo, SandraMadoz-Gúrpide, JuanRovira Guerín, AnaAlbanell Mestres, JoanRojo, FedericoLluch, AnaEroles, Pilar2020-04-242020-04-242019Tormo E, Ballester S, Adam-Artigues A, Burgués O, Alonso E, Bermejo B, et al. The miRNA-449 family mediates doxorubicin resistance in triple-negative breast cancer by regulating cell cycle factors. Sci Rep. 2019 Mar 29;9 (1):5316. DOI: 10.1038/s41598-019-41472-y2045-2322http://hdl.handle.net/10230/44316The mechanisms of chemotherapy resistance in triple negative breast cancer remain unclear, and so, new molecules which might mediate this resistance could optimize treatment response. Here we analyzed the involvement of the miRNA-449 family in the response to doxorubicin. The cell viability, cell-cycle phases, and the expression of in silico target genes and proteins of sensitive/resistant triple negative breast cancer cell lines were evaluated in response to doxorubicin treatment and after gain/loss of miRNAs-449 function achieved by transient transfection. Triple negative breast cancer patients were selected for ex vivo experiments and to evaluate gene and miRNAs expression changes after treatment, as well as survival analysis by Kaplan-Meier. Doxorubicin treatment upregulated miRNAs-449 and DNA-damage responder factors E2F1 and E2F3 in triple negative breast cancer sensitive breast cancer cells, while expression remained unaltered in resistant ones. In vitro overexpression of miRNAs-449 sensitized cells to the treatment and significantly reduced the resistance to doxorubicin. These changes showed also a strong effect on cell cycle regulation. Finally, elevated levels of miRNA-449a associated significantly with better survival in chemotherapy-treated triple negative breast cancer patients. These results reveal for the first time the involvement of the miRNA-449 family in doxorubicin resistance and their predictive and prognostic value in triple negative breast cancer patients.application/pdfengCopyright © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Mama -- Càncer -- Aspectes genèticsMama -- Càncer -- Tractamentinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41598-019-41472-yinfo:eu-repo/semantics/openAccess