Expression Patterns of Deubiquitinating Enzymes in Paclitaxel-Treated Lung Cancer Cells

Lung cancer remains a leading cause of cancer-related mortality, underscoring the urgent need for more effective therapeutic strategies, particularly due to the frequent development of drug resistance. Paclitaxel, a widely used chemotherapeutic agent for non-small cell lung cancer (NSCLC), often faces resistance that limits its clinical efficacy. Therefore, identifying molecular markers that modulate paclitaxel responsiveness is critical. The ubiquitin-proteasome system (UPS), which regulates protein homeostasis, plays a role in cancer progression, apoptosis, and drug resistance, with deubiquitinating enzymes (DUBs), serving as key regulators. Recent studies suggest that targeting specific DUBs may enhance drug sensitivity. This study aimed to investigate the expression patterns of DUB genes in response to paclitaxel treatment. Multiplex RT-PCR and RT-qPCR analysis revealed that USP1, USP5, USP28, and USP34 were downregulated, whereas USP10 and USP36 were upregulated in paclitaxel-treated A549 cells. Western blot analysis confirmed changes in protein levels consistent with mRNA expression for all DUBs except USP10 and USP36, which displayed discordant patterns. Furthermore, paclitaxel-induced apoptosis was verified by altered levels of apoptotic and antiapoptotic proteins including PARP, caspase-3, Bax, Bcl-2, Bcl-XL, and p53. The identification of these DUB genes highlights their potential as biomarkers for predicting drug responsiveness and prognosis during paclitaxel treatment, thereby proposing a new direction for improving the therapeutic efficacy of paclitaxel in NSCLC.