The Effects of miR-526b, miR655 and COX-2 Overexpression on Oxidative and Genotoxic Stress in MCF7 Breast Cancer Cells

Breast cancer progression and therapeutic resistance are influenced by the tumor’s ability to adapt to cellular stress, including oxidative damage and chemotherapeutic pressure. Two microRNAs, miR-526b and miR-655, have been shown to promote aggressive breast cancer phenotypes, such as enhanced proliferation, migration, invasion, cancer stem cell characteristics, and metastatic potential, through the activation of the COX-2/EP4/PI3K/Akt signaling pathway. Notably, overexpression of these miRNAs increases total intracellular reactive oxygen species (ROS) production. At the same time, exposure to modest levels of hydrogen peroxide (H₂O₂) further enhances their expression, suggesting a positive feedback loop between oxidative stress and miRNA activity. While their role in driving tumor aggressiveness is established, their influence on therapeutic outcomes remains underexplored. This project investigates how the overexpression of miR-526b, miR-655, and COX-2 in breast cancer cells alters cellular responses to both oxidative stress and the chemotherapeutic agent doxorubicin. By examining how these factors contribute to stress adaptation and drug resistance, the study aims to uncover key mechanisms underlying tumor progression and chemoresistance, with potential implications for improving treatment strategies.