IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
miRNAs expression profile induced by CtBP1 protein is critical for tumor growth and progression of breast cancer associated to metabolic syndrome
Autor/es:
FARRÉ, PL; DALTON, GN; SCALISE, G; MASSILLO, C; DE SIERVI, A; DUCA, RB; DE LUCA, P; PORRETTI, J; BERARDINO, B
Lugar:
Mar del Plata
Reunión:
Congreso; LXI Reunión de la Sociedad Argentina de Investigación Clínica; 2016
Institución organizadora:
Sociedad Argentina de Investigación Clínica, Sociedad Argentina de Inmunología, Sociedad Argentina de Farmacología Experimental, Sociedad Argentina de Nanomedicina y Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio
Resumen:
Breast cancer (BrCa) is the leading cause of cancer death in women and metabolic syndrome (MeS) constitutes a risk factor for this disease. C-terminal binding protein 1 (CtBP1) is a co-repressor of tumor suppressors activated by low NAD+/NADH ratio. Recently, we generated a MeS-like experimental model by chronically feeding mice with high fat diet. We found that CtBP1 and MeS induced breast carcinogenesis and tumor growth. Since miRNAs function as master regulators of cellular processes, the aim of this work was to identify the miRNA expression profile associated to BrCa in MeS mice.GeneChip miRNA 4.0 (Affymetrix) were hybridized to RNA from CtBP1-depleted or control MDA-MB-231 xenografts generated in MeS mice. After data normalization, we identified 42 CtBP1 regulated miRNAs. Gene ontology analysis of miRNAs predicted target genes determined using the bioinformatic tool ChemiRs, revealed enrichment in several biological processes, such as fatty acid biosynthetic process, cell cycle, cell migration and epithelial to mesenchymal transition. Furthermore using miRSystem tool we identified several CtBP1-regulated miRNAs involved in tumor growth (miR-381-3p, miR-146a-5p and miR-378a-3p) and tumor progression (miR-223-3p, miR-146a-5p, miR-494-3p, miR-381-3p, miR-433-3p, miR-522-3p, miR-940, miR-378a-3p). To validate these results we assessed miRNAs expression levels in CtBP1-depleted or control MDA-MB-231 xenografts by miRNA-RT-qPCR. CtBP1 induced miR-146a-5p and let7e-3p expression while repressed the expression of miR-378a-3p. Finally, we also generated 4T1-derived allografts in Balb/c mice with MeS or control, and miRNAs expression in tumor samples analyzed by miRNA-RT-qPCR showed that MeS induced miR-378a-3p, miR-146a-5p and let-7e-3p. These results show that both, CtBP1 and MeS, drives miRNAs expression which might be helpful as biomarkers for diagnosis, management and therapy of BrCa patients.