MiR-578 and miR-573 as potential players in BRCA-related breast cancer angiogenesis
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Katia Danza1, Simona De Summa1, Rosamaria Pinto1, Brunella Pilato1, Orazio Palumbo2, Giuseppe Merla2, Gianni Simone3 and Stefania Tommasi1
1 IRCCS “Giovanni Paolo II”, Molecular Genetics Laboratory – Bari, Italy
2 IRCCS Casa Sollievo della Sofferenza, Medical Genetics Unit – San Giovanni Rotondo (FG), Italy
3 IRCCS “Giovanni Paolo II”, Anatomopathology Unit – Bari, Italy
Stefania Tommasi, email:
Keywords: miR-573, miR-578, BRCA, familial breast cancer, angiogenesis
Received: July 02, 2014 Accepted: September 24, 2014 Published: September 25, 2014
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.
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