Cardiovascular Research Center, USA; Metabolic Disease Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Metabolic Disease Research, Departments of Pharmacology, Microbiology and Immunology, Lewis Katz School of Medicine at Temple University, Philadelphia, PA 19140, USA.
Pharmacol Ther. 2021 Apr;220:107715. doi: 10.1016/j.pharmthera.2020.107715. Epub 2020 Oct 24.
Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs characterized by a covalently closed-loop structure generated through a special type of alternative splicing termed back-splicing. Currently, an increasing body of evidence has demonstrated that 1) majority of circRNAs are evolutionarily conserved across species, stable, and resistant to RNase R degradation, and often exhibit cell-specific, and tissue-specific/developmental-stage-specific expression and can be largely independent of the expression levels of the linear host gene-encoded linear RNAs; 2) the biogenesis of circRNAs via back-splicing is different from the canonical splicing of linear RNAs; 3) circRNA biogenesis is regulated by specific cis-acting elements and trans-acting factors; 4) circRNAs regulate biological and pathological processes by sponging miRNAs, binding to RNA-binding protein (RBP), regulators of splicing and transcription, modifiers of parental gene expression, and regulators of protein translation or being translated into peptides in various diseases; 5) circRNAs have been identified for their enrichment and stability in exosomes and detected in body fluids such as human blood, saliva, and cerebrospinal fluids, suggesting that these exo-circRNAs have potential applications as disease biomarkers and novel therapeutic targets; 6) several circRNAs are regulated by oxidative stress and mediate reactive oxygen species (ROS) production as well as promote ROS-induced cellular death, cell apoptosis, and inflammation; 7) circRNAs have also emerged as important regulators in atherosclerotic cardiovascular disease, metabolic disease, and cancers; 8) the potential mechanisms of several circRNAs have been described in diseases, hinting at their potential applications as novel therapeutic targets. In this highlight, we summarized the current understandings of the biogenesis and functions of circRNAs and their roles in ROS regulation and vascular inflammation-associated with cardiovascular and metabolic disease. (Word count: 272).
环状 RNA(circRNAs)是一类新型的内源性非编码 RNA,其特征是通过一种特殊的称为反向剪接的选择性剪接产生共价闭环结构。目前,越来越多的证据表明:1)大多数 circRNAs 在物种间具有进化保守性,稳定且不易被核糖核酸酶 R 降解,通常表现出细胞特异性、组织特异性/发育阶段特异性表达,并且在很大程度上独立于线性宿主基因编码的线性 RNA 的表达水平;2)circRNA 通过反向剪接的生物发生不同于线性 RNA 的经典剪接;3)circRNA 的生物发生受特定顺式作用元件和反式作用因子调控;4)circRNA 通过海绵 miRNA、与 RNA 结合蛋白(RBP)结合、调节剪接和转录的因子、调节亲本基因表达的调节剂以及调节蛋白质翻译或在各种疾病中翻译为肽来调节生物学和病理过程;5)circRNAs 在 exosomes 中被鉴定为丰富和稳定,并在体液中检测到,如人血液、唾液和脑脊液,表明这些外泌体 circRNAs 具有作为疾病生物标志物和新型治疗靶点的潜力;6)一些 circRNAs 受到氧化应激的调节,并介导活性氧(ROS)的产生,以及促进 ROS 诱导的细胞死亡、细胞凋亡和炎症;7)circRNAs 也已成为动脉粥样硬化性心血管疾病、代谢性疾病和癌症的重要调节因子;8)几种 circRNAs 在疾病中的潜在机制已被描述,提示其作为新型治疗靶点的潜在应用。在这篇综述中,我们总结了 circRNAs 的生物发生和功能及其在 ROS 调节和与心血管和代谢疾病相关的血管炎症中的作用的最新认识。(单词数:272)