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Circular RNAs are a novel type of non-coding RNAs in ROS regulation, cardiovascular metabolic inflammations and cancers
Pharmacology & Therapeutics ( IF 12.0 ) Pub Date : 2020-10-24 , DOI: 10.1016/j.pharmthera.2020.107715
Fatma Saaoud 1 , Charles Drummer I V 1 , Ying Shao 1 , Yu Sun 1 , Yifan Lu 1 , Keman Xu 1 , Dong Ni 1 , Xiaohua Jiang 1 , Hong Wang 2 , Xiaofeng Yang 3
Affiliation  

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)



中文翻译:

环状 RNA 是一种新型的非编码 RNA,可用于 ROS 调节、心血管代谢炎症和癌症

环状 RNA (circRNA) 是一类新型的内源性非编码 RNA,其特征在于通过称为反向剪接的特殊类型的选择性剪接产生的共价闭环结构。目前,越来越多的证据表明:1)大多数 circRNA 在物种间进化上是保守的、稳定的、对 RNase R 降解具有抗性,并且经常表现出细胞特异性和组织特异性/发育阶段特异性表达,并且可以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)通过反向剪接的circRNAs的生物发生不同于线性RNAs的规范剪接;3)circRNA 的生物发生受特定的顺式作用元件和反式作用因子的调节;4) circRNAs通过海绵化miRNA、与RNA结合蛋白(RBP)结合、剪接和转录的调节剂、亲本基因表达的调节剂以及蛋白质翻译或被翻译成各种疾病中的肽的调节剂来调节生物和病理过程;5)已鉴定出circRNA在外泌体中的富集和稳定性,并在人体血液、唾液和脑脊液等体液中检测到,表明这些exo-circRNA具有作为疾病生物标志物和新型治疗靶点的潜在应用;6)几种 circRNA 受氧化应激的调节,介导活性氧 (ROS) 的产生,并促进 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、代谢疾病和癌症的重要调节因子;8)几种 circRNA 在疾病中的潜在机制已经被描述,暗示了它们作为新的治疗靶点的潜在应用。在这个亮点中,我们总结了目前对 circRNA 的生物发生和功能的理解,以及它们在 ROS 调节和与心血管和代谢疾病相关的血管炎症中的作用。(字数:272)

更新日期:2020-10-29
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