靶向甲羟戊酸途径抗血液肿瘤的研究进展

Research progress of targeting mevalonate pathway in hematologic malignancies

甲羟戊酸(mevalonate,MVA)途径是胆固醇合成的核心代谢通路,该途径异常参与多种肿瘤发生发展。羟甲基戊二酰辅酶A还原酶(3-hydroxy-3-methylglutaryl-CoA reductase,HMGCR)、羟甲基戊二酰辅酶A合酶1(3-hydroxy-3-methylglutaryl-CoA synthase 1,HMGCS1)及固醇调节元件结合蛋白2(sterol regulatory element binding protein 2,SREBP2)是MVA途径关键限速蛋白,能够在基因转录、蛋白质翻译和降解等过程中被精细调控。本文围绕MVA途径调控网络关键代谢酶、其与血液肿瘤的关系以及相关调节剂在血液肿瘤中的应用进行综述。

Mevalonate(MVA)pathway is the core metabolic pathway of cholesterol synthesis.Abnormal MVA pathway is involved in the occurrence and development of various tumors.3-Hydroxy-3-methylglutaryl-CoA reductase(HMGCR),3-hydroxy-3-methylglutaryl-CoA synthase 1(HMGCS1)and sterol regulatory element binding protein 2(SREBP2)are the key rate-limiting proteins in the MVA pathway,which can be precisely regulated in gene transcription,protein translation and degradation.This article reviews the key metabolic enzymes of the MVA pathway regulatory network,their relationship with hematologic malignancies,and the application of their regulators in hematologic malignancies.