Expression of microRNAs ‘let-7d and miR-195’ and Apoptotic Genes ‘BCL2 and Caspase-3’ as Potential Biomarkers of Female Breast Carcinogenesis

Abstract

Objective: Breast cancer (BC) is the most common cause of cancer-related death among women worldwide. Let-7d and microRNA-195 (miR-195) are members of microRNAs that are known tumor suppressors and are involved in the regulation of apoptosis, invasion, and other cellular functions. However, the roles of these microRNAs in BC progression remain controversial. This study aimed to explore the correlation between the expression of let-7d and miR-195 and apoptosis-related genes (ARGs) “B-cell lymphoma 2 (BCL2) and caspase-3 (CASP3)” as potential biomarkers of breast carcinogenesis. Methods: It was a retrospective case-control study in which expression of let-7d, miR-195, CASP3, and BCL2 was assessed using quantitative real-time PCR (qRT-PCR); and immunohistochemical (IHC) staining was used to determine expression of BCL2 and CASP3 in BC tissue versus normal breast tissue (NT) samples. Results: The expression of let-7d and miR-195 was significantly reduced within BC tissues compared to NT (P: < 0.0001); and there was a statically positive correlation between them (r=0.314, P: 0.005). They have also been correlated to biomarkers’ expression of genes related to apoptosis. There was a statistically significant positive association between CASP3, and both let-7d, and miR-195 relative gene expression (r=0.713, P: <0.0001 and r=0.236, P: 0.03, respectively). In contrast, there was a statistically significant negative association between the relative gene expression of BCL2, with let-7d, and miR-195 (r=-0.221, P: 0.04 and r=-0.311, P: 0.005, respectively). Conclusion: Let-7d and miR-195 have been suggested to be involved in BC through modulation of the ARGs including BCL2 and CASP3. The qRT-PCR and IHC studies demonstrated that decreased expression of let-7d and miR-195 prohibits apoptosis via downregulating CASP3 and increasing BCL2 expressions promoting BC progression. These results also hypothesize that let-7d and miR-195 along with apoptotic biomarkers (BCL2 and CASP3) can be used in the future to introduce novel, non-invasive molecular biomarkers for BC into clinical practice.