title: miR-151-5p, targeting chromatin remodeler SMARCA5, as a marker for the BRCAness phenotype.
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.
authors.affiliation: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
authors.affiliation: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Pinto
authors.affiliation: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Danza
authors.affiliation: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors.forename: Brunella
authors.initials: B
authors.lastname: Pilato
authors.affiliation: IRCCS 'Casa Sollievo della Sofferenza', Medical Genetics Unit, San Giovanni Rotondo (FG), Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Palumbo
authors.affiliation: IRCCS 'Casa Sollievo della Sofferenza', Medical Genetics Unit, San Giovanni Rotondo (FG), Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Micale
authors.affiliation: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: De Summa
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D061986:MCF-7 Cells; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D002868:Chromosomal Proteins, Non-Histone; C548886:MIRN151a microRNA, human; D035683:MicroRNAs; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human
keywords: BRCAness; DNA repair; breast cancer; miR-151-5p; microRNA profiling