Expression of microRNAs ‘let-7d and miR-195’ and Apoptotic Genes ‘BCL2 and Caspase-3’ as Potential Biomarkers of Female Breast Carcinogenesis
Basma A. Ibrahim 1
, Abdelmonem Awad Hegazy 2,3,*, Mai Ahmed Gobran 4, Mohamed Abdallah Zaitoun 5, Fayig Elmigdadi 2, Gehane A. El-Gindy 6, Salwan Abdelmonem Hegazy 7, Elsayed M. Alashkar 8 and Walaa E. Omar 11Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Zagazig University, Zagazig City 44519, Egypt.
2Basic Medical and Dental Sciences Department, Faculty of Dentistry, Zarqa University, Zarqa City 13110, Jordan.
3Human Anatomy and Embryology Department, Faculty of Medicine, Zagazig University, Zagazig City 44519,, Egypt.
4Pathology Department, Faculty of Medicine, Zagazig University, Zagazig City 44519, Egypt.
5General Surgery Department, Faculty of Medicine, Zagazig University, Zagazig City 44519, Egypt.
6Clinical Pharmacology Department, Faculty of Medicine, Mutah University, Alkarak 61710, Jordan.
7Dermatology Department, Faculty of Medicine, Zagazig University, Zagazig, Zagazig City 44519, Egypt.
8Physics Department, Faculty of Science, Al-Azhar University, Nasr City 11765, Egypt.
Corresponding Author E-mail: ahegazy@zu.edu.jo
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.
Keywords: Apoptotic Biomarkers; Breast Cancer; Immunohistochemistry; Micrornas; Novel Molecular Markers Back to TOC