CONICET | Buscador de Institutos y Recursos Humanos

Breast cancer (BrCa) is the main cause of death by cancer in womenworldwide. Metabolic syndrome (MeS) is an important risk factorin the development of BrCa, since it correlates with high grade tumors,increased recurrence and metastasis progression. miRNAsare non-coding RNAs that silence the expression of mRNAs andcan be released to bloodstream. The aim of this work was to identifynew biomarkers based on circulating miRNAs for diagnosis of BrCaassociated to MeS. Balb/c mice (n=30) were chronically fed withhigh fat (HFD) or control (CD) diets. After 15 weeks, 10 animals ofeach group were inoculated s.c. with 4T1 cells on the mammaryfat pad. When tumors were palpable, 5 HFD and 5 CD mice weresacrificed (Early Stage=ES). The remaining animals were sacrificedwhen tumors reached a volume around 600 mm3 (AdvancedStage=AS) together with the non-tumor group (Control=C). Bloodand tumors samples were collected for RNA isolation. The expressionof several miRNAs associated to BrCa or MeS were analyzedby stem-loop RT-qPCR. We identified two groups of BrCa and MeSassociated miRNAs in allografts: one group of miRNAs (miR-125b-5p, miR-21-5p, miR-106b-5p, miR-221-3p, miR-34a-5p) was increasedin mice with AS BrCa compared to ES tumors. The othergroup of miRNAs (miR-10b-5p, miR-138-5p, miR-143-3p, miR-127-3p, miR-205-5p, miR-146a-5p, miR-195-5p) was diminished in micewith AS BrCa compared to ES tumors. Remarkably, MeS increasedmiR-195-5p and diminished miR-146a-5p expression at ES BrCa.We also identified circulating miRNAs in plasma from mice: i) miR-10b-5p was downregulated in AS vs C plasma; ii) miR-195-5p andmiR-106b-5p were upregulated in HFD vs CD fed mice in ES; iii)miR-195-5p and miR-106b-5p were downregulated in HFD vs CDin AS; and iv) miR-21-5p, miR-125b-5p, miR-138-5p, miR-205-5p,miR-146a-5p and miR-221-3p were upregulated in HFD vs CD inES.