Hsa-miR-155-5p Up-Regulation in Breast Cancer and Its Relevance for Treatment With Poly[ADP-Ribose] Polymerase 1 (PARP-1) Inhibitors
Pasculli, Barbara (Fondazione IRCCS Casa Sollievo Della Sofferenza. Laboratorio di Oncologia)
Barbano, Raffaela (Fondazione IRCCS Casa Sollievo Della Sofferenza. Laboratorio di Oncologia)
Fontana, Andrea (Fondazione IRCCS Casa Sollievo Della Sofferenza)
Biagini, T. (Fondazione IRCCS Casa Sollievo Della Sofferenza. Laboratory of Bioinformatics Unit)
Di Viesti, M. P. (Department of Medicine. Scuola Medica Salernitana," University of Salerno)
Rendina, M. (Fondazione IRCCS Casa Sollievo Della Sofferenza. Laboratorio di Oncologia)
Valori, V. M. (Fondazione IRCCS Casa Sollievo Della Sofferenza. UO di Oncologia. San Giovanni Rotondo)
Morritti, M. (Fondazione IRCCS Casa Sollievo Della Sofferenza. UO di Oncologia. San Giovanni Rotondo)
Bravaccini, Sara (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS. Biosciences Laboratory)
Ravaioli, S. (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS. Biosciences Laboratory)
Maiello, Evaristo (Fondazione IRCCS Casa Sollievo Della Sofferenza. UO di Oncologia. San Giovanni Rotondo)
Graziano, Paolo (Fondazione IRCCS Casa Sollievo Della Sofferenza)
Murgo, R. (Fondazione IRCCS Casa Sollievo Della Sofferenza)
Copetti, Massimiliano (Fondazione IRCCS Casa Sollievo Della Sofferenza)
Mazza, T. (Fondazione IRCCS Casa Sollievo Della Sofferenza. Laboratory of Bioinformatics Unit)
Fazio, V. M. (Fondazione IRCCS Casa Sollievo Della Sofferenza. Laboratorio di Oncologia)
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Parrella, Paola (Fondazione IRCCS Casa Sollievo Della Sofferenza. Laboratorio di Oncologia)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Olaparib ; PARP-1 inhibitors ; Breast cancer ; Homologous recombination ; Hsa-miR-155-5p
Publicat a:	Frontiers in Oncology, Vol. 10 (december 2020) , p. 1415, ISSN 2234-943X

DOI: 10.3389/fonc.2020.01415
PMID: 32903519

14 p, 1.4 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Institut de Recerca contra la Leucèmia Josep Carreras
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