Mir‐301b‐3p Targets Alx4 to Suppress Cisplatin Sensitivity in Breast Cancer through DNA Damage

OBJECTIVE: To elucidate how ALX Homeobox 4 (ALX4) modulates cisplatin sensitivity via DNA damage regulation in breast cancer (BC), this study explored the established role of mRNA-mediated DNA repair in driving chemoresistance. METHODS: Integrated bioinformatics and molecular experiments identified ALX4 and miR-301b-3p expression patterns in BC cells. Potential binding sites between them were predicted and verified by dual-luciferase assays. Cellular experiments determined cisplatin IC50 via CCK-8 assays, while functional impacts of the miR-301b-3p/ALX4 axis on proliferation, apoptosis, and cisplatin-induced DNA damage were assessed using CCK-8, flow cytometry, alkaline comet assays, and western blot. RESULTS: Our study identified downregulated ALX4 and upregulated miR-301b-3p in BC tissues. miR-301b-3p directly targeted ALX4, as confirmed by dual-luciferase assays. Overexpression of ALX4 inhibited BC cell proliferation, promoted apoptosis, enhanced cisplatin-induced DNA damage, and increased cisplatin sensitivity. Conversely, miR-301b-3p negatively regulated ALX4, thereby modulating DNA damage and cellular response to cisplatin. CONCLUSION: This study demonstrates that miR-301b-3p promotes BC proliferation and reduces cisplatin sensitivity by suppressing ALX4, a mechanism mediated through the regulation of DNA damage pathways. These findings offer new insights into cisplatin resistance and suggest potential therapeutic targets for overcoming chemoresistance in BC.