Pasculli, BarbaraBarbano, RaffaelaFontana, AndreaBiagini, TommasoViesti, Maria Pia DiRendina, MichelinaValori, Vanna MariaMorritti, MariaBravaccini, SaraRavaioli, SaraMaiello, EvaristoGraziano, PaoloMurgo, RobertoCopetti, MassimilianoMazza, TommasoFazio, Vito MicheleEsteller, Manel, 1968-Parrella, Paola2021-03-252021-03-252020-08-122234-943Xhttps://hdl.handle.net/2445/175775miR-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.14 p.application/pdfengcc-by (c) Pasculli, Bárbara et al., 2020http://creativecommons.org/licenses/by/3.0/esCàncer de mamaInhibidors enzimàticsOncogensBreast cancerEnzyme inhibitorsOncogenesinfo:eu-repo/semantics/article7041812021-03-25info:eu-repo/semantics/openAccess32903519