TP63-MIR205HG axis suppresses triple-negative breast cancer progression by inhibiting autophagy

Background Triple-negative breast cancer (TNBC) is an aggressive subtype with few therapies. The primary objective of this investigation was to pinpoint autophagy-associated genes with prognostic value and to elucidate the functional roles of the TP63-MIR205HG axis within the context of TNBC. Methods Autophagy-associated genes curated in the Human Autophagy Database were intersected with differentially expressed genes (DEGs) derived from The Cancer Genome Atlas. Prognostic significance was evaluated by Kaplan-Meier analysis. Co-expression analysis was performed using cBioPortal, and MIR205HG expression was validated via ENCORI. The TP63-MIR205HG regulatory relationship was examined by qRT-PCR, dual-luciferase reporter assay, and ChIP-qPCR. The autophagy markers LC3B and p62 proteins were evaluated using western blotting. Functional consequences were assessed using CCK-8 viability assays and Transwell migration assays. Results Fifteen autophagy-related DEGs were identified, of which TP63, IL24, and NKX2-3 were significantly associated with overall survival. TP63 showed the strongest correlation with MIR205HG (Spearman r = 0.43, p < 0.001). MIR205HG was downregulated in breast cancer, and low expression correlated with poor survival. Mechanistically, TP63 bound to MIR205HG, promoting its transcriptional activity. TP63 knockdown promoted autophagy (increased LC3B-II/I ratio, decreased p62), while MIR205HG overexpression reversed this effect. Functional rescue experiments demonstrated that MIR205HG overexpression attenuated TP63 knockdown-induced proliferation, migration, and invasion. Conclusion The TP63-MIR205HG axis suppresses TNBC progression through autophagy inhibition, offering potential therapeutic targets.