NAT10 promotes cisplatin resistance and immune escape by increasing the expression of DUSP1 and PD-L1 in gastric cancer - PubMed
5 hours ago
- #NAT10
- #Gastric Cancer
- #Cisplatin Resistance
- NAT10 catalyzes mRNA modification via ac4C and is linked to tumor progression and chemotherapy resistance.
- Elevated NAT10 levels promote cisplatin resistance in gastric cancer cells, while knockdown enhances cisplatin sensitivity both in vitro and in vivo.
- NAT10 binds to DUSP1 mRNA, catalyzing ac4C modification at specific CDS sites to increase mRNA stability and protein abundance.
- NAT10 mediates cisplatin-induced apoptosis resistance through DUSP1 via the JNK and ERK signaling pathways.
- NAT10 upregulates PD-L1 expression via FOSB, contributing to immune escape in gastric cancer.
- Combining a NAT10 inhibitor with an anti-PD-1 antibody synergistically improves antitumor efficacy against cisplatin-resistant gastric cancer in murine models.
- These findings highlight NAT10 as a potential therapeutic target to reverse cisplatin resistance and enhance immunotherapy in gastric cancer.