MiR-578 and miR-573 as potential players in BRCA-related breast cancer angiogenesis.
Oncotarget
; 6(1): 471-83, 2015 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-25333258
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
MicroARNs
/
Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Oncotarget
Año:
2015
Tipo del documento:
Article
País de afiliación:
Italia