biostudies-literatureWei XNatural Science Foundation of Fujian ProvinceNational Natural Science Foundation of ChinaRP96445https://www.ebi.ac.uk/biostudies/studies/S-EPMC11458174biostudies-literatureUnknown13Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. Despite the widespread recognition of tumor immunotherapy in treating unresectable GC, challenges, including ineffective immunotherapy and drug resistance, persist. Therefore, understanding the regulatory mechanisms of PD-L1, particularly in the context of super-enhancers (SEs) and zinc finger protein 36 ring finger protein-like 1 (ZFP36L1) RNA-binding protein, is crucial. In this study, we performed H3K27ac Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, investigated the heterogeneity of SEs between two GC subtypes with differential growth patterns, and revealed the immune escape signatures driven by ZFP36L1-SE in infiltrative GC through SEs inhibitors treatment. The regulation of ZFP36L1 to PD-L1 waeLifeSuper-enhancer-driven ZFP36L1 promotes PD-L1 expression in infiltrative gastric cancer.PMC11458174No. 2023J011594No. 2021J02056No. 2020CXB048No. 822728942021D026No. 81871979Liu JXie WHou JZhuo HCai JWei XLin LWang KCheng JCai WfalseSuper-enhancer-driven ZFP36L1 promotes PD-L1 expression in infiltrative gastric cancer.Gastric cancer (GC) is a major cause of cancer-related mortality worldwide. Despite the widespread recognition of tumor immunotherapy in treating unresectable GC, challenges, including ineffective immunotherapy and drug resistance, persist. Therefore, understanding the regulatory mechanisms of PD-L1, particularly in the context of super-enhancers (SEs) and zinc finger protein 36 ring finger protein-like 1 (ZFP36L1) RNA-binding protein, is crucial. In this study, we performed H3K27ac Cleavage Under Targets and Tagmentation (CUT&Tag) sequencing, investigated the heterogeneity of SEs between two GC subtypes with differential growth patterns, and revealed the immune escape signatures driven by ZFP36L1-SE in infiltrative GC through SEs inhibitors treatment. The regulation of ZFP36L1 to PD-L1 wa2024-01-01T00:00:00Z2024 Oct2026-07-15T04:03:38.565Z2025-04-04T01:54:34.524ZS-EPMC114581743937363010.7554/eLife.96445