环状RNA与氧化应激互作机制的研究进展

doi:10.3969/j.issn.1674-8115.2022.03.020

摘要/Abstract

摘要：

环状RNA（circular RNA，circRNA）是一类共价闭环非编码RNA，广泛存在于各组织细胞中，具有重要的生物学功能。circRNA可通过与RNA结合蛋白相互作用、调节mRNA稳定性、作为竞争性内源RNA等机制，在转录或转录后水平发挥调控作用。氧化应激即体内活性氧的产生与清除失衡的一种状态，在多种疾病的发生、发展过程中起着重要作用。近期研究表明，多种circRNA在氧化应激状态下存在表达差异，并通过充当微RNA海绵等机制，调控相关炎症因子和凋亡基因的表达，进而干预氧化应激状态下细胞的存活及凋亡情况。根据调控作用结果，有circRNA可参与氧化应激造成的损伤，起到促氧化应激作用；也有circRNA通过上调抗氧化基因，降低氧化应激的影响，起到抗氧化应激作用；circRNA与氧化应激相互作用、彼此影响，共同参与多种疾病的发生和发展。该文从氧化应激概述、circRNA在各系统疾病氧化应激中的作用、circRNA与氧化应激潜在互作机制等方面进行综述，以期为相关研究提供参考。

关键词: 环状RNA, 氧化应激, 微RNA

Abstract:

Circular RNA (circRNA) is a class of covalent closed-loop non-coding RNA, existing widely in various tissue and having important biological functions. circRNA can play a regulatory role at the transcriptional or post-transcriptional level by interacting with RNA-binding proteins, regulating mRNA stability and acting as competitive endogenous RNAs. Oxidative stress, a state in which there is an imbalance between the accumulation and removal of reactive oxygen species (ROS) in the body, plays an important role in the onset and development of many diseases. Under oxidative stress conditions, numerous recent studies have shown that differentially expressed circRNA regulate the expression of inflammatory factors and apoptotic genes by acting as miRNA sponges, thereby interfering with cell survival and apoptosis. According to the regulatory effects, circRNA can participate in the damage caused by oxidative stress and play a pro-oxidative stress role. circRNA can also play an anti-oxidative stress role by upregulating antioxidant genes and reducing the effects of oxidative stress. circRNA and oxidative stress interact and induce each other, and mutually they participate in the occurrence and development of a variety of diseases. This paper reviews the relevant literature from the overview of oxidative stress, the role of circRNA under oxidative stress in different systemic diseases, and the potential mechanism of circRNA-oxidative stress interactions, aiming to provide reference for further research.

Key words: circRNA, oxidative stress, miRNA

中图分类号:

赵久红, 童佳婷, 沈郅珺, 吕叶辉. 环状RNA与氧化应激互作机制的研究进展[J]. 上海交通大学学报（医学版）, 2022, 42(3): 393-399.

ZHAO Jiuhong, TONG Jiating, SHEN Zhijun, LÜ Yehui. Research progress in the mechanism of interactive regulation between circular RNA and oxidative stress[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(3): 393-399.

图/表 4

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Type	Marker	Abbreviation	Trend
Protease	Superoxide dismutase	SOD	↓
	Glutathione peroxidase	GSH-Px	↓
	Inducible nitric oxide synthase	iNOS	↑
	Catalase	CAT	↓
Intermediate product	Reactive oxygen species	ROS	↑
	Nitric oxide	NO	↑
	Oxidized glutathione	GSSG	↑
	3-Nitrotyrosine	3-NT	↑
End product	8-Hydroxy-2-deoxyguanosine	8-OHdG	↑
End product	Malondialdehyde	MDA	↑

Type	Marker	Abbreviation	Trend
Protease	Superoxide dismutase	SOD	↓
	Glutathione peroxidase	GSH-Px	↓
	Inducible nitric oxide synthase	iNOS	↑
	Catalase	CAT	↓
Intermediate product	Reactive oxygen species	ROS	↑
	Nitric oxide	NO	↑
	Oxidized glutathione	GSSG	↑
	3-Nitrotyrosine	3-NT	↑
End product	8-Hydroxy-2-deoxyguanosine	8-OHdG	↑
End product	Malondialdehyde	MDA	↑

Pre-treatment	Oxidative stress marker	circRNA				Ref.
Pre-treatment	Oxidative stress marker	ID	Trend	Regulatory mechanism	Function	Ref.
H₂O₂	‒	circNCX1	↑	miR-133a-3p↓； CDIP1↑	Pro-apoptotic	［19］
H₂O₂	‒	circHIPK2	↑	miR-485-5p↓； ATG101↑	Pro-apoptotic	［20］
ox-LDL	ROS， SOD， MDA， iNOS	circTM7SF3 circ_0007478	↑	miR-206↓； ASPH， TNF-α， IL-6↑	Pro-inflammatory Pro-apoptotic	［21］
HG	ROS， SOD， MDA	circBPTF	↑	miR-384↓； LIN28B， TNF-α， IL-6， IL-1β， Bax， caspase3↑	Pro-inflammatory Pro-apoptotic	［22］
LPS	ROS， SOD， MDA， iNOS	circHIPK3	↑	TNF-α， IL-6， Bax， CK-MB↑	Pro-inflammatory Pro-apoptotic	［23］
I/R	SOD， MDA	circB4GALT2 circ_0000064	↓	CK-MB， Bax， caspase3↑	Pro-apoptotic	［24］
ox-LDL	SOD， MDA	circSMARCA5 circ_0001445	↓	miR-640↑； TNF-α， IL-6， IL-β， Bax， caspase3↑	Anti-inflammatory Anti-apoptotic	［25］
ox-LDL	‒	circRSF1 circ_0000345	↓	miR-758↑； CCND2↓； Bax， HIF-1α↑	Anti-apoptotic	［26］［27］
ox-LDL	‒	circCHFR circ_0029589	↑	miR-424-5p↓； IGF-2↑	Anti-apoptotic	［28］

Pre-treatment	Oxidative stress marker	circRNA				Ref.
Pre-treatment	Oxidative stress marker	ID	Trend	Regulatory mechanism	Function	Ref.
H₂O₂	‒	circNCX1	↑	miR-133a-3p↓； CDIP1↑	Pro-apoptotic	［19］
H₂O₂	‒	circHIPK2	↑	miR-485-5p↓； ATG101↑	Pro-apoptotic	［20］
ox-LDL	ROS， SOD， MDA， iNOS	circTM7SF3 circ_0007478	↑	miR-206↓； ASPH， TNF-α， IL-6↑	Pro-inflammatory Pro-apoptotic	［21］
HG	ROS， SOD， MDA	circBPTF	↑	miR-384↓； LIN28B， TNF-α， IL-6， IL-1β， Bax， caspase3↑	Pro-inflammatory Pro-apoptotic	［22］
LPS	ROS， SOD， MDA， iNOS	circHIPK3	↑	TNF-α， IL-6， Bax， CK-MB↑	Pro-inflammatory Pro-apoptotic	［23］
I/R	SOD， MDA	circB4GALT2 circ_0000064	↓	CK-MB， Bax， caspase3↑	Pro-apoptotic	［24］
ox-LDL	SOD， MDA	circSMARCA5 circ_0001445	↓	miR-640↑； TNF-α， IL-6， IL-β， Bax， caspase3↑	Anti-inflammatory Anti-apoptotic	［25］
ox-LDL	‒	circRSF1 circ_0000345	↓	miR-758↑； CCND2↓； Bax， HIF-1α↑	Anti-apoptotic	［26］［27］
ox-LDL	‒	circCHFR circ_0029589	↑	miR-424-5p↓； IGF-2↑	Anti-apoptotic	［28］

Pre-treatment	Oxidative stress marker	circRNA				Ref.
Pre-treatment	Oxidative stress marker	ID	Trend	Regulatory mechanism	Function	Ref.
Paraquat	‒	circSLC8A1	↑	SLC8A1↓	Pro-apoptotic	［32］
Glu	ROS	circFoxO3	↑	BimEL， cytochrome， caspase3↑	Pro-apoptotic	［33］
CSE	ROS， SOD， MDA	circASCC3 circ_0006872	↑	miR-145-5p↓； NF-κB↑	Pro-inflammatory Pro-apoptotic	［12］
CSE	ROS， SOD， MDA	circANKRD11	↑	miR-145-5p↓； Bax， caspase3， TNF-α， IL-6， IL-β↑	Pro-inflammatory Pro-apoptotic	［34］
CSE	SOD， MDA	circRBMS1	↑	miR-197-3p↓； Bax， TNF-α， IL-β， FBXO11↑	Pro-inflammatory Pro-apoptotic	［35］
H₂O₂	‒	circPRKCI	↓	miR-545/miR-589↑； E2F7↓； caspase3， caspase9↑	Anti-apoptotic	［36］