2026-04-13T02:27:54Zhttps://recercat.cat/oai/requestoai:recercat.cat:2445/1757752025-12-05T09:34:09Zcom_2072_1057col_2072_478799col_2072_478917
Hsa-miR155-5p up-regulation in Breast Cancer and its relevance for treatment with Poly [ADP-ribose] polymerase 1 (PARP-1) inhibitors
Pasculli, Barbara
Barbano, Raffaela
Fontana, Andrea
Biagini, Tommaso
Viesti, Maria Pia Di
Rendina, Michelina
Valori, Vanna Maria
Morritti, Maria
Bravaccini, Sara
Ravaioli, Sara
Maiello, Evaristo
Graziano, Paolo
Murgo, Roberto
Copetti, Massimiliano
Mazza, Tommaso
Fazio, Vito Michele
Esteller, Manel
Parrella, Paola
Càncer de mama
Inhibidors enzimàtics
Oncogens
Breast cancer
Enzyme inhibitors
Oncogenes
miR-155-5p is a well-known oncogenic microRNA, showing frequent overexpression in human malignancies, including breast cancer. Here, we show that high miR-155-5p levels are associated with unfavorable prognostic factors in two independent breast cancer cohorts (CSS cohort, n = 283; and TCGA-BRCA dataset, n = 1,095). Consistently, miR-155-5p results as differentially expressed in the breast cancer subgroups identified by the surrogate molecular classification in the CSS cohort and the PAM50 classifier in TCGA-BRCA dataset, with the TNBC and HER2-amplified tumors carrying the highest levels. Since the analysis of TCGA-BC dataset also demonstrated a significant association between miR-155-5p levels and the presence of mutations in homologous recombination (HR) genes, we hypothesized that miR-155-5p might affect cell response to the PARP-1 inhibitor Olaparib. As expected, miR-155-5p ectopic overexpression followed by Olaparib administration resulted in a greater reduction of cell viability as compared to Olaparib administration alone, suggesting that miR-155-5p might induce a synthetic lethal effect in cancer cells when coupled with PARP-1-inhibition. Overall, our data point to a role of miR-155-5p in homologous recombination deficiency and suggest miR-155-5p might be useful in predicting response to PARP1 inhibitors in the clinical setting.
2021-03-25T16:17:36Z
2021-03-25T16:17:36Z
2020-08-12
2021-03-25T16:17:36Z
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Reproducció del document publicat a: https://doi.org/10.3389/fonc.2020.01415
Frontiers In Oncology, 2020, vol. 10
https://doi.org/10.3389/fonc.2020.01415
cc-by (c) Pasculli, Bárbara et al., 2020
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
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Articles publicats en revistes (Ciències Fisiològiques)