In silico analysis revealed hsa-miR-19a-3p and hsa-miR-19b-3p as two potential inhibitors of EGF mRNA in Breast Cancer

Abstract

Breast cancer (BrC) is a highly prevalent and often fatal disease affecting both women and, to a lesser extent, men worldwide. There were about 2.3 million new breast cancer cases worldwide in 2020, resulting in approximately 685,000 deaths. According to the American Cancer Society data, 42,250 women are estimated to die due to breast cancer in the year 2024. A major focus of current research in breast cancer prognosis revolves around chemotherapy, radiotherapy, hormonal therapy, and so on. However, microRNAs (miRNAs) have recently emerged as therapeutic agents, inhibiting pathological pathways by targeting specific cancer-related genes. In this study, we analyzed differentially expressed genes (DEGs) from four datasets of BrC patients to identify potential miRNA to block pathways associated with highly expressed DEGs. The Epidermal Growth Factor (EGF) gene was found to be a common factor in most of these datasets, indicating its potential importance in breast cancer. The overexpression of Epidermal Growth Factor Receptor (EGFR) has been observed in numerous breast cancer patients. The overexpression of EGFR occurs when EGF binds with the receptor and activates it. The activation and overexpression of EGFR eventually leads to the initiation of two common pathways named: PI3K/AKT/mTOR (PAM) pathway and Ras/Raf/MEK/ERK signaling pathway which promotes tumor growth, invasion, and metastasis in breast cancer. In order to inhibit BrC cell growth, we explored potential miRNAs targeting the EGF gene mRNA. Two miRNAs identified by our analysis bind to the conserved region at the 3' UTR of the EGF gene mRNA, namely hsa-miR-19a-3p and hsa-miR-19b-3p. Perhaps inhibiting the EGF activity might effectively inhibit EGFR activation and consequently impede the initiation of pathological pathways in breast cancer using these miRNAs. Overall, our study highlights the importance of the EGF gene in breast cancer and suggests using miRNAs hsa-miR-19a-3p and hsa-miR-19b-3p to inhibit its activity. However, further research is required to fully comprehend the mechanisms underlying the EGF gene's role in cancer development and progression.