Evaluation of tumorigenesis-related miRNAs in breast cancer in Egyptian women: a retrospective, exploratory analysis

Abstract

Breast cancer (BC) is a leading cause of global female cancer-related deaths, despite treatment advancements. A growing focus on investigating microRNA-based therapeutics and their role in BC progression. A computational analysis was performed to identify the potential miRNA–mRNA network involved in the BC pathogenesis and assist with the treatment strategy. Then, the expression levels of five circulatory miRNAs (miR-200a-3p, miR-124-3p, miR-205-5p, miR-15a-5p, and miR-155-5p) were assessed by using qRT-PCR in 75 BC patients (early-stage: n = 26 and late-stage: n = 49) and 20 healthy controls. The analysis included various (a) stages (early and late) and (b) receptor statuses (ER + ve & HER2 -ve), (HER + ve & ER -ve), and triple-negative (TNBC). In-silico analysis suggested that STAT3 serves as an efficacy biomarker suppressed by miR-124-3p. Additionally, the miR-155-5p showed the ability to activate CTNNB1 which acts as a biomarker for BC progression, to inhibit DNA repair genes (ARID2, and WEE1), and the transcriptional factor gene (TCF4). MiR-205-5p and miR-16 suppressed VEGFA expression, a survival factor for BC. MiR-200a-3p, miR-205-5p, and miR-124-3p showed downregulation in the serum of BC patients compared to controls. The ROC analysis of those miRNAs demonstrated their significant diagnostic accuracy for identifying BC patients. Additionally, miR-155-5p exhibited a significant upregulation in TNBC and can be used as an indicative marker for TNBC. This study holds significant promise for the development of noninvasive miRNA biomarkers with potential clinical applications.