Hsa-miR155-5p 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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Bibliographic Details
Authors: 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, 1968-, Parrella, Paola
Format: article
Status:Published version
Publication Date:2020
Country:España
Institution:Universidad de Barcelona
Repository:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/175775
Online Access:https://hdl.handle.net/2445/175775
Access Level:Open access
Keyword:Càncer de mama
Inhibidors enzimàtics
Oncogens
Breast cancer
Enzyme inhibitors
Oncogenes
Description
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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