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三羧酸循环(tricarboxylic acid cycle,TCA)是氧化磷酸化和合成代谢产物的主要途径,与细胞生长、修复和增殖有关。琥珀酸脱氢酶(succinate dehydrogenase,SDH)则是其中的一种关键酶。近年来发现多种肿瘤中存在SDH基因突变,这些突变特异性地使酶功能丧失,导致琥珀酸在细胞内堆积,与α-酮戊二酸(α-KG)竞争性抑制组蛋白去甲基化酶和DNA去甲基化酶等多种α-KG依赖的双加氧酶的活性,影响细胞内的表观调控,这些代谢表型的改变与肿瘤的发生、发展、预后等密切相关。研究SDH基因在肿瘤中的作用,有助于将其作为肿瘤早期诊断、预后评估和靶向治疗的标志性基因。
Tricarboxylic acid cycle (TCA) is the main pathway of oxidative phosphorylation and anabolism of metabolites, which is related to cell growth, repair and proliferation. Succinate dehydrogenase (succinate dehydrogenase, SDH) is one of the key enzymes. In recent years, a variety of tumors found in SDH gene mutations, these mutations specifically enable the loss of enzyme function, resulting in the accumulation of succinic acid in cells, and α-ketoglutaric acid (α-KG) competitive inhibition of histone demethyl Enzymes and DNA demethylase and other α-KG-dependent dioxygenase activity, affecting the intracellular expression and regulation of these metabolic phenotypes and tumor occurrence, development, prognosis are closely related. Studying the role of SDH in the tumor helps to use it as a landmark gene for early diagnosis, prognosis evaluation and targeted therapy of tumors.