ABSTRACT
Micro-RNAs (miRs) constitute a class of small noncoding RNAs implicated in the regulation of gene expression by binding to target mRNAs. A miR can target several mRNAs, being involved in different biologic processes and pathologies. This pleiotropic function might explain the link between diseases co-occurrence. Epigenetic origin of the link between obesity and breast cancer (BC) is investigated in a cohort of Tunisian patients, focusing on polymorphism at germline level (miR-146a) and on expression in mammary tumors (miR-21, miR-146a, and miR-34a), according to body mass index (BMI) and clinico-pathologic features. The measure of miR expression in 60 mammary tumors was realized using quantitative RT-PCR. Study of rs 2910164 in miR-146a was performed by PCR and direct sequencing using blood DNA of 83 affected women and 50 unrelated subjects from Great Tunis. MiR-21, miR-146a, and miR-34a have been quantified in breast tumor according to BMI. MiR-21 is significantly more expressed in tumors of obese women comparatively to nonobese patients. On the contrary, miR-34a is decreased in tumors of obese women. Moreover, in obese BC patients, a significant increase in both miR-21 and miR-146a expression is revealed in cases with lymph node metastasis. The polymorphism at rs 2910164 (miR-146a) locus was not shown as a risk factor for BC. However the mutant CC genotype was revealed to be associated with a risk for bad outcome of the disease. Chronic inflammation in obese women would be linked to aggressive breast tumors via induction of oncomiRs overexpression and decrease of tumor suppressor miRs.
