TGFbeta and miRNA regulation in familial and sporadic breast cancer
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Katia Danza1,*, Simona De Summa1,*, Rosamaria Pinto1, Brunella Pilato1, Orazio Palumbo2, Massimo Carella2, Ondina Popescu3, Maria Digennaro4, Rosanna Lacalamita1 and Stefania Tommasi1
1IRCCS ‘Giovanni Paolo II’, Molecular Genetics Laboratory, Bari 70124, Italy
2IRCCS ‘Casa Sollievo della Sofferenza’, Medical Genetics Unit, San Giovanni Rotondo 71013, Italy
3IRCCS ‘Giovanni Paolo II’, Anatomopathology Unit, Bari 70124, Italy
4IRCCS ‘Giovanni Paolo II’, Experimental Medical Oncology Unit, Bari 70124, Italy
*These authors have contributed equally to this work
Stefania Tommasi, email: [email protected]
Keywords: breast cancer, TGF-β pathway, BRCA1, ATM, miRNA
Received: November 04, 2016 Accepted: December 27, 2016 Published: January 30, 2017
The term ‘BRCAness’ was introduced to identify sporadic malignant tumors sharing characteristics similar to those germline BRCA-related. Among all mechanisms attributable to BRCA1 expression silencing, a major role has been assigned to microRNAs. MicroRNAs role in familial and sporadic breast cancer has been explored but few data are available about microRNAs involvement in homologous recombination repair control in these breast cancer subgroups. Our aim was to seek microRNAs associated to pathways underlying DNA repair dysfunction in breast cancer according to a family history of the disease. Affymetrix GeneChip microRNA Arrays were used to perform microRNA expression analysis in familial and sporadic breast cancer. Pathway enrichment analysis and microRNA target prediction was carried out using DIANA miRPath v.3 web-based computational tool and miRWalk v.2 database. We analyzed an external gene expression dataset (E-GEOD-49481), including both familial and sporadic breast cancers. For microRNA validation, an independent set of 19 familial and 10 sporadic breast cancers was used. Microarray analysis identified a signature of 28 deregulated miRNAs. For our validation analyses by real time PCR, we focused on miR-92a-1*, miR-1184 and miR-943 because associated to TGF-β signalling pathway, ATM and BRCA1 genes expression. Our results highlighted alterations in miR-92a-1*, miR-1184 and miR-943 expression levels suggesting their involvement in repair of DNA double-strand breaks through TGF-beta pathway control.
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