IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Aberrant miRNAs expression profile induced by metabolic syndrome in mammary gland might be critical for breast carcinogenesis
Autor/es:
DE LUCA, PAOLA; DALTON, GUILLERMO N.; FARRÉ, PAULA L.; DE LUCA, PAOLA; DE SIERVI, ADRIANA; DALTON, GUILLERMO N.; PORRETTI, JULIANA; FARRÉ, PAULA L.; DUCA, ROCIO B.; DE SIERVI, ADRIANA; PORRETTI, JULIANA; MASSILLO, CINTIA; DUCA, ROCIO B.; SCALISE, GEORGINA D.; GRAÑA, KAREN D.; MASSILLO, CINTIA; SCALISE, GEORGINA D.; GRAÑA, KAREN D.
Lugar:
C.A.B.A
Reunión:
Congreso; Reunión Conjunta de Sociedades de Biociencias 2017; 2017
Institución organizadora:
Sociedad Argentina de Investigación Clínica
Resumen:
Breast cancer (BrCa) is the most common malignant neoplasm and the leading cause of cancer female death in the world, excluding skin cancers. Metabolic Syndrome (MeS) is a risk factor for BrCa that and increase its aggressiveness and metastasis. Recently, we generated a MeS experimental model by chronically feeding mice with a high fat diet which induced alterations in the mammary glands such as an increase of postnatal development and prominent duct patterns. These ducts showed high expression of CtBP1, a tumor suppressor gene that is activated by low NAD+/NADH ratio. Moreover, we found that CtBP1 and MeS increased breast tumor growth and progression modulating the expression of 42 miRNAs involved in cell proliferation and tumor progression. The aim of this work was to identify the miRNA expression profile induced by MeS in normal mammary glands. We selected a panel of miRNAs obtained from the miRNA microarray analysis to determine expression levels in samples of mammary tissue from mice with MeS or control using RT-qPCR stem loop metodology: miR-378a-3p, miR-146a-5p, miR-223-3p, miR-381-5p, miR-433-3p, miR-194-1-5p.We found that MeS significantly repressed the expression of miR-194-1-5p while induced miR-433-3p in mammary tissue. Using the bioinformatics tool ChemiRs, that integrates the information of ten miRNAs databases, we analyzed the molecular pathways modulated by these miRNAs. We found that miR-194-1-5p and miR-433-3p are involved in several molecular pathways including cancer, metabolism, developmental biology, adherent junction and apoptosis. Finally, evaluating microarray datasets from cBioPortal, we demonstrated that miR-194-1-5p presented DNA amplification in 20 % of BrCa patients. Altogether, these results suggest that MeS induces an aberrant miRNA expression profile that could be critical in breast carcinogenesis.