2. Academic Validation
  3. CSDE1-mediated histone lactylation modification of the HOXD9 promoter promotes gastric cancer progression

CSDE1-mediated histone lactylation modification of the HOXD9 promoter promotes gastric cancer progression

  • Biochem Pharmacol. 2026 Jul:249:117918. doi: 10.1016/j.bcp.2026.117918.
Hongyu Zhang 1,  Xiaokun Wang 2,  Nan Sun 3,  Zhen Wang 1,  Chunlin Zhao 1,  Songcheng Yin 4,  Leli Zeng 5,  Yawei Zhang 6,  Yang Fu 7
Affiliations

Affiliations

  • 1 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 2 Department of Thyroid and Vascular Surgery, Jingzhou Hospital Affiliated to Yangtze University, Jingzhou, China.
  • 3 Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • 4 Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China.
  • 5 Digestive Diseases Center, Guangdong Provincial Key Laboratory of Digestive Cancer Research, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China. Electronic address: [email protected].
  • 6 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: [email protected].
  • 7 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Electronic address: [email protected].
PMID: 41864431 DOI: 10.1016/j.bcp.2026.117918
Abstract

Recent research has underscored the crucial role of dysregulated RNA-binding proteins (RBP) in the onset and advancement of gastric Cancer. Cold shock domain containing E1 (CSDE1), functioning as an RBP, has emerged as an essential contributor to this process, although its specific mechanistic roles in GC are still not fully understood. Immunohistochemistry was performed on human gastric Cancer tissue microarrays to assess CSDE1 expression. Extracellular acidification rate, glucose uptake, and lactate production assays were conducted to measure glycolytic activity. RNA immunoprecipitation assays were used to examine the interaction between CSDE1 and Lactate Dehydrogenase A (LDHA) mRNA. Chromatin immunoprecipitation assays were performed to detect lactylation modification at the H3K18 site within the Homeobox D9 (HOXD9) promoter region. In vitro cell assays and in vivo xenograft experiments were conducted to evaluate the biological functions of CSDE1. Our findings indicate that CSDE1 is significantly upregulated in gastric Cancer tissues and correlated with poor prognosis. CSDE1 enhances LDHA mRNA stability, leading to increased glycolytic activity and lactate production. The lactate generated promotes HOXD9 transcription through H3K18 lactylation, thereby facilitating gastric Cancer progression. Thus, CSDE1 drives gastric Cancer progression through the LDHA-lactate-H3K18 lactylation-HOXD9 axis. CSDE1 promotes metabolic reprogramming in gastric Cancer by enhancing lactate production and downstream epigenetic signaling. Its overexpression predicts poor prognosis, highlighting CSDE1 as both a potential biomarker and a therapeutic target for improving gastric Cancer outcomes.

Keywords

CSDE1; Gastric cancer; Glycolysis; Lactylation.

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