Moreno Cerena, Santos Ruben Mercado, Burns Robert, Zhang Wen Cai
Department of Cancer Division, Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, 6900 Lake Nona Blvd, Orlando, FL 32827, USA.
Cancers (Basel). 2020 Nov 3;12(11):3237. doi: 10.3390/cancers12113237.
Succinate dehydrogenase (SDH) complex connects both the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC) in the mitochondria. However, mutation or dysfunction-induced succinate accumulation results in multiple cancers and non-cancer diseases. The mechanistic studies show that succinate activates hypoxia response and other signal pathways via binding to 2-oxoglutarate-dependent oxygenases and succinate receptors. Recently, the increasing knowledge of ribonucleic acid (RNA) networks, including non-coding RNAs, RNA editors, and RNA modifiers has expanded our understanding of the interplay between SDH and RNA networks in cancer and other diseases. Here, we summarize recent discoveries in the RNA networks and their connections to SDH. Additionally, we discuss current therapeutics targeting SDH in both pre-clinical and clinical trials. Thus, we propose a new model of SDH-RNA network interaction and bring promising RNA therapeutics against SDH-relevant cancer and other diseases.
琥珀酸脱氢酶（SDH）复合体连接线粒体中的三羧酸（TCA）循环和电子传递链（ETC）。然而，突变或功能障碍导致的琥珀酸积累会引发多种癌症和非癌症疾病。机制研究表明，琥珀酸通过与2-酮戊二酸依赖性加氧酶和琥珀酸受体结合来激活缺氧反应及其他信号通路。近来，对包括非编码RNA、RNA编辑器和RNA修饰剂在内的核糖核酸（RNA）网络的认识不断增加，拓展了我们对SDH与RNA网络在癌症及其他疾病中相互作用的理解。在此，我们总结了RNA网络中的最新发现及其与SDH的联系。此外，我们还讨论了临床前和临床试验中针对SDH的现有疗法。因此，我们提出了一种SDH-RNA网络相互作用的新模型，并带来了针对与SDH相关的癌症及其他疾病的有前景的RNA疗法。
