TRIM33 Reverses Cisplatin Resistance in Non-Small Cell Lung Cancer by Regulating the PI3K/AKT Pathway via Ubiquitination-Mediated Degradation of LPCAT1

Background: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for 80-85% of cases. Cisplatin (DDP) is a first-line chemotherapy drug for NSCLC, but acquired DDP resistance severely limits therapeutic efficacy. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is involved in tumor progression, but its role in DDP resistance of NSCLC remains unclear. This study aimed to investigate the regulatory mechanism of LPCAT1 in DDP-resistant NSCLC and explore the potential role of tripartite motif-containing 33 (TRIM33) in modulating LPCAT1. Methods: -test, one-way analysis of variance (ANOVA), and Student-Newman-Keuls test, with P < 0.05 considered statistically significant. Results: experiments confirmed that LPCAT1 promoted DDP resistance and tumor growth, while TRIM33 overexpression reversed this phenotype. Conclusion: TRIM33 regulates LPCAT1 stability through ubiquitination-mediated degradation, thereby suppressing PI3K/AKT signaling and glycolysis and attenuating DDP resistance in NSCLC. These findings suggest that the TRIM33-LPCAT1 axis may represent a potential therapeutic candidate for DDP-resistant NSCLC and provide a basis for further investigation of strategies to improve DDP sensitivity.