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miR-151-5p, targeting chromatin remodeler SMARCA5, as a marker for the BRCAness phenotype

2016; Impact Journals LLC; Volume: 7; Issue: 49 Linguagem: Inglês

10.18632/oncotarget.10345

1949-2553

Stefania Tommasi, Rosamaria Pinto, Katia Danza, Brunella Pilato, Orazio Palumbo, Lucia Micale, Simona De Summa,

DNA Repair Mechanisms

// Stefania Tommasi 1 , Rosamaria Pinto 1 , Katia Danza 1 , Brunella Pilato 1 , Orazio Palumbo 2 , Lucia Micale 2 and Simona De Summa 1 1 IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy 2 IRCCS 'Casa Sollievo della Sofferenza', Medical Genetics Unit, San Giovanni Rotondo (FG), Italy Correspondence to: Stefania Tommasi, email: // Keywords : breast cancer, BRCAness, microRNA profiling, DNA repair, miR-151-5p Received : April 21, 2016 Accepted : June 13, 2016 Published : June 30, 2016 Abstract In recent years, the assessment of biomarkers useful for "precision medicine" has been a hot topic in research. The involvement of microRNAs in the pathogenesis of breast cancer has been highly investigated with the aim of being able to molecularly stratify this highly heterogeneous disease. Our aim was to identify microRNAs targeting DNA repair machinery, through Affymetrix GeneChip miRNA Arrays, in a cohort of BRCA-related and sporadic breast cancers. Moreover, we analyzed microRNA expression taking into account our previous results on the expression of PARP1, because of its importance in targeted therapy. miR-361-5p and miR-151-5p were found to be overexpressed in PARP1-upregulating BRCA-germline mutated and sporadic breast tumors. Pathway enrichment analysis was performed to identify potential target genes to be analyzed in the validation step in an independent cohort. Our results confirmed the overexpression of miR-151-5p and, interestingly, its role in the targeting of SMARCA5, a chromatin remodeler. This result was also confirmed in vitro , both through luciferase assay and by analyzing endogenous levels of SMARCA5 in MCF-7 cell lines using miR-151-5p mimic and inhibitor. In conclusion, our data showed the possibility of considering the overexpression of PARP1 and miR-151-5p as biomarkers useful to correctly treat sporadic breast cancers, which eventually could be considered as BRCAness tumors, with PARP-inhibitors.