Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors

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 dat...

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Authors: Pasculli, Barbara|||0000-0002-3333-0255; Barbano, Raffaela|||0000-0002-4533-4157; Fontana, Andrea|||0000-0002-6660-5315; Biagini, T.; Di Viesti, M. P.; Rendina, M.; Valori, V. M.; Morritti, M.; Bravaccini, Sara|||0000-0002-0075-8538; Ravaioli, S.; Maiello, Evaristo|||0000-0003-3890-3435; Graziano, Paolo|||0000-0001-7066-7896; Murgo, R.; Copetti, Massimiliano|||0000-0002-7960-5947; Mazza, Tommaso|||0000-0003-0434-8533; Fazio, V. M.; Esteller, M.|||0000-0003-4490-6093; Parrella, Paola|||0000-0001-6031-9636
Format: Article
Publication date:2020
Country:España
Institution:Universitat Autònoma de Barcelona
Repository:Dipòsit Digital de Documents de la UAB
Language:English
OAI Identifier:oai:ddd.uab.cat:236578
Online Access:https://ddd.uab.cat/record/236578
https://dx.doi.org/urn:doi:10.3389/fonc.2020.01415
Access Level:Open access
Keyword:Olaparib
PARP-1 inhibitors
Breast cancer
Homologous recombination
Hsa-miR-155-5p
Summary: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.

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