Aberrant miRNAs expression profile induced by metabolic syndrome in the mammary gland might be critical for breast carcinogenesis.

GRAÑA K; DUCA RB; FARRÉ PL; SCALISE G; PORRETTI J; DALTON GN; MASSILLO C; DE SIERVI A

C.A.B.A.

Congreso; Reunión conjunta de sociedades de biociencias; 2017

Sociedad Argentina de Investigación Clínica

Abstract: Breast cancer (BrCa) is the most common malignantneoplasm and the leading cause of cancer female death in theworld, excluding skin cancers. Metabolic Syndrome (MeS) is a riskfactor for BrCa that and increase its aggressiveness and metastasis.Recently, we generated a MeS experimental model by chronicallyfeeding mice with a high fat diet which induced alterations in themammary glands such as an increase of postnatal development andprominent duct patterns. These ducts showed high expression ofCtBP1, a tumor suppressor gene that is activated by low NAD+/NADH ratio. Moreover, we found that CtBP1 and MeS increasedbreast tumor growth and progression modulating the expression of42 miRNAs involved in cell proliferation and tumor progression. Theaim of this work was to identify the miRNA expression profile inducedby MeS in normal mammary glands.We selected a panel of miRNAs obtained from the miRNA microarrayanalysis to determine expression levels in samples of mammarytissue from mice with MeS or control using RT-qPCR stem loopmetodology: miR-378a-3p, miR-146a-5p, miR-223-3p, miR-381-5p,miR-433-3p, miR-194-1-5p.We found that MeS significantly repressedthe expression of miR-194-1-5p while induced miR-433-3pin mammary tissue. Using the bioinformatics tool ChemiRs, that integratesthe information of ten miRNAs databases, we analyzed themolecular pathways modulated by these miRNAs. We found thatmiR-194-1-5p and miR-433-3p are involved in several molecularpathways including cancer, metabolism, developmental biology, adherentjunction and apoptosis. Finally, evaluating microarray datasetsfrom cBioPortal, we demonstrated that miR-194-1-5p presentedDNA amplification in 20 % of BrCa patients.Altogether, these results suggest that MeS induces an aberrantmiRNA expression profile that could be critical in breast carcinogenesis.