Circulating miRNAs as biomarkers associated to breast cancer and metabolic syndrome.

FARRÉ PL; DALTON GN; PICCIONI F; MASSILLO CL; SCALISE G; DE LUCA P; DE SIERVI A

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 main cause of death by cancer in women worldwide. Metabolic syndrome (MeS) is an important risk factor in the development of BrCa, since it correlates with high grade tumors, increased recurrence and metastasis progression. miRNAs are non-coding RNAs that silence the expression of mRNAs and can be released to bloodstream. The aim of this work was to identify new biomarkers based on circulating miRNAs for diagnosis of BrCa associated to MeS.Balb/c mice (n=30) were chronically fed with high fat (HFD) or control (CD) diets. After 15 weeks, 10 animals of each group were inoculated s.c. with 4T1 cells on the mammary fat pad. When tumors were palpable, 5 HFD and 5 CD mice were sacrificed (Early Stage=ES). The remaining animals were sacrificed when tumors reached a volume around 600 mm3 (Advanced Stage=AS) together with the non-tumor group (Control=C). Blood and tumors samples were collected for RNA isolation. The expression of several miRNAs associated to BrCa or MeS were analyzed by stem-loop RT-qPCR.We identified two groups of BrCa and MeS associated miRNAs in allografts: one group of miRNAs (miR-125b-5p, miR-21-5p, miR-106b-5p, miR-221-3p, miR-34a-5p) was increased in mice with AS BrCa compared to ES tumors. The other group 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 mice with AS BrCa compared to ES tumors. Remarkably, MeS increased miR-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 and miR-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 CD in 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 in ES.