Hypoxia-inducible factor 1-alpha and lactate dehydrogenase-A axis in metabolic changes and aggression in esophageal squamous-cell carcinoma  

作　　者：Xia Chen Hai-Yan Liu Wu-Bi Zhou Li-Li Zhang Jian Huang Da-Wei Bao 

机构地区：[1]Department of Pathology,The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University,Huai’an 223300,Jiangsu Province,China

出　　处：《World Journal of Gastrointestinal Oncology》2025年第3期322-333,共12页世界胃肠肿瘤学杂志(英文)

摘　　要：BACKGROUND Esophageal squamous-cell carcinoma(ESCC)is a highly aggressive cancer,predominantly affecting populations in Eastern Asia and parts of Africa.Its pathogenesis is influenced by both genetic and environmental factors.Despite recent therapeutic advances,survival rates remain dismal,underscoring an urgent need for novel therapeutic targets.AIM To investigate the role of hypoxia-inducible factor 1-alpha(HIF1A)in the progression of ESCC and its impact on the metabolic enzyme lactate dehydrogenase A(LDHA),which is crucial for the glycolytic pathway in hypoxic tumor environments.METHODS Utilizing transcriptomic data from multiple public databases,we analyzed differential gene expression and conducted gene ontology and transcription factor network analyses.The regulatory impact of HIF1A on LDHA was specifically examined through integrative analysis with HIF1A ChIP-seq data and confirmed via siRNA-mediated knockdown experiments in ESCC cell lines.RESULTS Our findings reveal a significant upregulation of HIF1A in ESCC tissues,associated with poor prognosis.HIF1A directly regulates LDHA,enhancing glycolysis under hypoxic conditions and contributing to tumor aggressiveness.Knockdown of HIF1A in cell lines not only reduced LDHA expression but also altered key pathways related to cell cycle and apoptosis.CONCLUSION The critical role of the HIF1A-LDHA axis in ESCC highlights its potential as a therapeutic target,underscoring the need for future clinical trials to validate the efficacy of HIF1A inhibitors in enhancing treatment outcomes.

关 键 词：Esophageal squamous-cell carcinoma Hypoxia-inducible factor 1-alpha Lactate dehydrogenase A Metabolic reprogramming Therapeutic target 

分 类 号：R735.1[医药卫生—肿瘤]