title: MiR-578 and miR-573 as potential players in BRCA-related breast cancer angiogenesis.
abstract: The involvement of microRNA (miRNAs), a new class of small RNA molecules, in governing angiogenesis has been well described. Our aim was to investigate miRNA-mediated regulation of angiogenesis in a series of familial breast cancers stratified by BRCA1/2 mutational status in BRCA carriers and BRCA non-carriers (BRCAX). Affymetrix GeneChip miRNA Arrays were used to perform miRNA expression analysis on 43 formalin-fixed paraffin-embedded (FFPE) tumour tissue familial breast cancers (22 BRCA 1/2-related and 21 BRCAX). Pathway enrichment analysis was carried out with the DIANA miRPath v2.0 web-based computational tool, and the miRWalk database was used to identify target genes of deregulated miRNAs. An independent set of 8 BRCA 1/2-related and 11 BRCAX breast tumors was used for validation by Real-Time PCR. In vitro analysis on HEK293, MCF-7 and SUM149PT cells were performed to best-clarify miR-573 and miR-578 role. A set of 16 miRNAs differentially expressed between BRCA 1/2-related and BRCAX breast tumors emerged from the profile analysis. Among these, miR-578 and miR-573 were found to be down-regulated in BRCA 1/2-related breast cancer and associated to the Focal adhesion, Vascular Endothelial Growth Factor (VEGF) and Hypoxia Inducible Factor-1 (HIF-1) signaling pathways. Our data highlight the role of miR-578 and miR-573 in controlling BRCA 1/2-related angiogenesis by targeting key regulators of Focal adhesion, VEGF and HIF-1 signaling pathways.
authors.affiliation: IRCCS "Giovanni Paolo II", Molecular Genetics Laboratory - Bari, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Danza
authors.affiliation: IRCCS "Giovanni Paolo II", Molecular Genetics Laboratory - Bari, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: De Summa
authors.affiliation: IRCCS "Giovanni Paolo II", Molecular Genetics Laboratory - Bari, Italy.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Pinto
authors.affiliation: IRCCS "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: Giuseppe
authors.initials: G
authors.lastname: Merla
authors.affiliation: IRCCS "Giovanni Paolo II", Anatomopathology Unit - Bari, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Simone
authors.affiliation: IRCCS "Giovanni Paolo II", Molecular Genetics Laboratory - Bari, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Tommasi
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; C585063:MIRN573 microRNA, human; D035683:MicroRNAs