| 中文关键词: 琥珀酸脱氢酶 甲基化 肿瘤 致癌代谢物 |
| 英文关键词:succinate dehydrogenase methylation neoplasms oncometabolites |
| 基金项目:浙江省自然基金重点项目（ LZ13H160002）；浙江省卫生高层次创新人才培养工程项目；浙江省新世纪151人才工程重点资助项目 |
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| 中文摘要: |
| 摘 要：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。 |
| 英文摘要: |
| Abstract：Tricarboxylic acid cycle(TCA) is the main pathway for oxidative phosphorylation and synthesis of metabolites，associated with cell growth，repair and proliferation.Succinate dehydrogenase(SDH) is the key enzyme in the TCA.Recently，SDH gene mutation was found in various tumors，inducing loss of the SDH enzyme function，resulting succinate accumulation in the cells.With the similar structure to α-ketoglutarate(α-KG)，succinate could competitively inhibit the activity of α-KG-dependent dioxygenases，including histone methyltransferase and DNA demethylase etc.，which will influence the epigenetic regulation，as the histone and DNA methylation in cell.These changes are closely related with the tumor occurrence，development and prognosis.We suspect that the SDH gene could be a tumor biomarker for diagnosis，prognosis and targeted therapy. |
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