Super-enhancer Activates Master Transcription Factor NR3C1 Expression and Promotes 5-FU Resistance in Gastric Cancer.

ABSTRACT: Poor response to 5-fluorouracil (5-FU) remains an obstacle in the treatment of gastric cancer (GC). Super enhancers (SEs) are crucial for determining tumor cell survival under drug pressure. SE landscapes related to 5-FU-resistance are mapped to GC using chromatin immunoprecipitation-sequencing (ChIP-Seq). SiRNA transcription factors (TFs) screen determines master TF Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) activated by SE. High NR3C1 expression driven by SE correlated with 5-FU resistance in patient-derived organoids (PDOs). Phase separation formed by NR3C1 is observed using fluorescence recovery after photobleaching (FRAP). NR3C1 protein and Mediator promoted SE-related gene transcription via phase separation. SEs and NR3C1 co-binding patterns are explored using Cleavage Und

SUBMITTER: Yu J 

PROVIDER: S-EPMC11831572 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature