Expression and polymorphism of micro-RNA according to body mass index and breast cancer presentation in Tunisian patients

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. K E Y W O R D Sbody mass index, mammary tumors, miR-146a, miR-21, miR-34a tions, transcription of these miRs is at baseline levels. In the context of inflammation, several stimuli such as cytokines (TNF-, IL-1 ) or ligands of TLR such LPS are capable of regulating the expression of these

A Review of Cancer Genetics and Genomics Studies in Africa

“…The contribution of epigenetic factors to risk and prognosis of breast cancer reported in Africa included the roles of tissue microRNA, circulating free mRNA, circulating long non-coding RNA ( 158 – 163 ) as well as DNA methylation status of breast cancer susceptibility genes like APC , ERα , RASSFIA , UCHL1 , COX-2 , and FHIT ( 161 , 164 – 167 ) in breast tumor across Africa.…”

Evidences from a Systematic Review and Meta-Analysis Unveil the Role of MiRNA Polymorphisms in the Predisposition to Female Neoplasms

“…The full texts of the remaining 79 records were evaluated and 10 articles were excluded for the following reasons: insufficient reported data ( n : 4) [16,17,18,19], studying other genes or polymorphisms ( n : 3) [20,21,22], not a case-control design ( n : 2) [23,24], and a duplicate study ( n : 1) [25]. Finally, a total of 69 articles remained [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85<...>…”

“…Twenty-eight association studies with a total of 11,071 cases and 12,312 controls were included in the meta-analysis of miR-146a rs2910164 and the risk of female neoplasms (Table 1 and Figure 2) [26,28,32,33,34,35,36,38,42,46,47,50,52,55,60,63,67,68,69,70,73,74,77,78,80,81,83,92]. Among these, there were studies that were carried out among Asians ( n : 20), Caucasians ( n : 5), Africans ( n : 1), or South Americans ( n : 1).…”

Current Landscape: The Mechanism and Therapeutic Impact of Obesity for Breast Cancer

“…Certain micro-RNAs (miRs) that participated in the regulation of inflammation are known as inflamma-miRs. A cohort study of Tunisian patients reported that chronic inflammation in obese BC patients was associated with aggressive BC by inducing overexpression of oncomiRs (such as miR-21 and miR146a) and reducing the expression of tumor suppressor miRs (such as miR-34a) ( 93 ). More comprehensive mechanism studies connecting obesity-driven inflammation with BC are needed for more potential therapeutic strategies of BC.…”