METABOLIC SYNDROME ALTERS THE EXPRESSION OF CRITICAL MIRNAS FOR BREAST CANCER DEVELOPMENT IN THE MAMMARY GLAND FROM METABOLIC SYNDROME MICE

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

Mar del Plata

Congreso; LXIII Reunión Annual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

Breast cancer (BrCa) is the first cancer in incidence and mortality inwomen in the world, excluding skin cancers. Metabolic Syndrome(MeS) is a risk factor for BrCa and increases its aggressiveness andmetastasis. Previously, we generated a MeS experimental model bychronically feeding mice with a high fat diet (HFD). This diet inducedalterations in the mammary glands such as prominent duct patternswith high expression of CTBP1, a tumor suppressor gene. Moreover,we found that CTBP1 and MeS increased tumor growth andprogression from MDA-MB-231 xenografts generated in athimic nu/nu mice modulating the expression of 42 miRNAs. Inflammation inducedby MeS is a crucial feature which impacts on cancer. The aimof this work was to assess the miRNA expression profile inducedby MeS in mammary glands from immunosuppressed and immunocompetentmice.We investigated MeS effect in mammary gland from nu/nu mice andimmunocompetent BALB/c mice fed with HFD or control diet. Thus,we determined expression levels by RT-qPCR of miR-378a-3p, miR-146a-5p, miR-223-3p, miR-381-5p, miR-433-3p, miR-194-1-5p andmiR-494-3p in mammary gland from mice fed with HFD or controldiet. MeS significantly repressed the expression of miR-194-1-5pwhile induced miR-433-3p in mammary tissue of nu/nu mice. On theother hand, MeS repressed the expression of miR-378a-3p in breasttissue of BALB/c mice. Using the bioinformatics tool ChemiRs, wefound that these miRNAs are involved in several molecular pathwaysincluding cancer, developmental biology, adherent junctionand apoptosis. Finally we evaluated the effect of these miRNAs onBrCa patients survival using the bioinformatics tool PROGmiRV2.We found that a low expression of miR-378a-5p increased survivalfree of metastasis and relapse, while low levels of miR-194-1-5p increasedsurvival free of relapse. Our results suggest that MeS altersmiRNA expression profile which could be critical in breast carcinogenesis.