circRNA_0005075 knockdown potentiates anti-PD-1 therapy in vivo, suggesting a therapeutic target for gastric cancer.
Abstract
Highlights • circRNA_0005075 drives histone lactylation via lactate metabolism, establishing a novel metabolic-epigenetic-immune axis in gastric cancer.• circRNA_0005075 knockdown reduces H3K9la at PD-L1 promoter, suppressing PD-L1 and enhancing T cell cytotoxicity.• circRNA_0005075 knockdown potentiates anti-PD-1 therapy in vivo, suggesting a therapeutic target for gastric cancer.
Although aerobic glycolysis is a hallmark of hepatocellular carcinoma (HCC) progression, the underlying epitranscriptomic mechanisms remain poorly understood. Here, we identify METTL15, an N4-methylcytidine (m4C) RNA methyltransferase, as a novel oncogenic driver of this metabolic reprogramming. METTL15 is significantl...
Longhui Xie, Ken Ning, Yu-Hu Wang et al.· International Journal of Bio...· 0 citations
ABSTRACT Metabolic reprogramming is a hallmark of gastric cancer (GC); however, the role of transcriptional regulators in modulating glycolysis remains incompletely understood. By integrating proteomic, transcriptomic, and CRISPR‐based functional screening datasets, we identified WDR12, a WD40‐family protein that is up...
Ru-Tong Zhang, De-Hua Liu, Xiao-Xi Feng et al.· Cancer Science· 0 citations
High-glycolytic iCAFs in the gastric cancer tumor microenvironment exhibit significant metabolic heterogeneity and can secrete large amounts of lactate through the reverse Warburg effect, thus constructing an immunosuppressive microenvironment. Lactic acid is transported into tumor cells via MCT1 and regulates PD-L1 ex...
E. Zhang· Explore Medical Science and...· 0 citations
Solid tumors are frequently characterized by hypoxia, which drives metabolic reprogramming toward glycolysis and increased lactate production. Beyond its role as a metabolic end product, lactate can influence gene regulation through histone lactylation, a recently identified post-translational modification linking cell...
Julia Ostapowicz, K. Kulcenty· Letters in Oncology Science· 0 citations
Histone lactylation is an epigenetic modification that connects lactate metabolism with protein function. Our study identified lactate enhances the protein lactylation level not only in Myeloid-derived suppressor cells (MDSCs) of tumor-bearing mice, but also in the tumor tissues of lung cancer patients. This modificati...
Yao Dai, Hai-Yan Dai, Ya-Hui Wang et al.· Cancer immunology research· 0 citations
Gastric cancer (GC) is one of the most common malignant tumors worldwide. Metabolic reprogramming and epigenetic dysregulation represent its key pathological characteristics. As a novel lactate-mediated post-translational modification, lactylation converts metabolic signals into epigenetic and protein functional regula...
Yu-Liang Fang, Peng Chen, Yu-Hong Gao et al.· Molecular Medicine Reports· 0 citations
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