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. (Università degli Studi di 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 (IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori "Dino Amadori")
Ravaioli, S. (IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori "Dino Amadori")
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, Tommaso (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

Fecha:	2020
Resumen:	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.
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Olaparib ; PARP-1 inhibitors ; Breast cancer ; Homologous recombination ; Hsa-miR-155-5p
Publicado en:	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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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
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