Targeting the NAT10/XIST/YAP1 Axis-Mediated Vascular Abnormalization Enhances Immune Checkpoint Blockade in Gastric Cancer.

ABSTRACT: Tumor vascular normalization has emerged as a promising strategy to potentiate immune checkpoint blockade in solid tumors. Here, we unveil a previously unrecognized NAT10/XIST/YAP1/VEGFA signaling axis driving vascular abnormalization in gastric cancer (GC) and demonstrate its therapeutic potential in remodeling the tumor immune microenvironment. Through integrative analysis of acetylated RNA immunoprecipitation sequencing (acRIP-seq) and functional validation, we identified NAT10-mediated N4-acetylcytidine (ac4C) modification as a critical stabilizer of lncRNA XIST. Mechanistically, XIST recruits hnRNPK to facilitate YAP1 nuclear translocation, thereby activating TEAD4-dependent VEGFA transcription and promoting angiogenic programming. Genetic or pharmacological inhibition of NAT10 with R

SUBMITTER: Lei X 

PROVIDER: S-EPMC12374829 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature