Regulatory Axis of circMYO9B and hsa-miR-3529-5p in modulating the breast Cancer biomarker MUC1

Abstract

Purpose: Breast cancer (BC) is the most prevalent and lethal cancer among women worldwide. Overexpression of the MUC1 gene is observed in approximately 40 of BC cases. Additionally, mucin-1-derived antigens are recognized as significant serum biomarkers for BC. Identifying genetic regulators of MUC1 may reveal novel pathways for managing and treating BC. This study investigates the regulatory relationship between circMYO9B, hsa-miR-3529-5p, and MUC1 expression. Methods: We utilized circAtlas, CircNet, and miRWalk databases to predict interactions between circMYO9B and hsa-miR-3529-5p and between hsa-miR-3529-5p and MUC1. RNA22 and RNAhybrid-BiBiServe2 confirmed an 82 high-binding affinity between hsa-miR-3529-5p and MUC1. Experimental validation included RT-qPCR to quantify circMYO9B, hsa-miR-3529-5p, and MUC1 expression levels. Functional assays were performed by constructing plasmids for circMYO9B, hsa-miR-3529-5p, and MUC1, transfecting them into HEK293T cells, and conducting dual luciferase reporter assays. Result: Our results demonstrate that circMYO9B interacts directly with hsa-miR-3529-5p, functioning as a sponge to regulate MUC1 expression in BC. This regulatory axis involving circMYO9B and hsa-miR-3529-5p provides insights into the molecular mechanisms underlying MUC1 dysregulation. MUC1, a key BC gene and marker, may be influenced by this interaction, emphasizing its potential as a target for therapeutic and diagnostic strategies. Subsequent cell viability assays confirmed that overexpression of miR-3529-5p significantly reduced MCF7 cell survival, suggesting an increase in apoptosis. Discussion: This study provides valuable insights into the molecular mechanisms underlying MUC1 regulation and emphasizes the importance of miR-3529 and circMYO9B in modulating MUC1 expression, which may have implications for targeted therapies and diagnostic strategies in breast cancer.