From resistance to sensitivity: the impact of FADD and lncRNA PPFIA1-AS1 on cisplatin treatment in LUSC.

Cisplatin resistance remains a significant challenge in treating lung squamous cell carcinoma (LUSC). The role of FADD in this resistance requires further investigation. Our study revealed that FADD is overexpressed in LUSC patients, correlating with lower survival rates. We also discovered that long-term cisplatin-resistant LUSC cell lines (LUSC-CR) had elevated FADD protein levels, and reducing FADD restored their cisplatin sensitivity. At the same time, LUSC-CR cells resisted cisplatin-induced DNA damage and had enhanced DNA repair, linked to P53's negative regulation of FADD. Additionally, knockdown of the long non-coding RNA (lncRNA) PPFIA1-AS1 can potentiate drug resistance in LUSC cells by decelerating FADD protein turnover and elevating FADD protein levels. In essence, this study elucidated novel mechanisms underlying cisplatin resistance in LUSC, wherein the PPFIA1-AS1/FADD axis regulates DNA damage and repair. Consequently, targeting the PPFIA1-AS1/FADD axis may present a promising avenue for overcoming cisplatin resistance and enhancing the prognosis of LUSC patients.