2023, Vol. 27 ›› Issue (8): 1286-1291

The regulatory role of circular RNAs in cerebral ischemia-reperfusion injury

Nie Chenchen1, Su Kaiqi1, Gao Jing1, 2, Fan Yongfu1, Ruan Xiaodi1, Yuan Jie1, Duan Zhaoyuan1, Feng Xiaodong1, 2   

Abstract: BACKGROUND: Ischemic stroke is a devastating cerebrovascular disease with high morbidity and mortality worldwide. Currently, clinical treatments for ischemic stroke have limited efficacies and its pathogenesis still needs to be further explored, which will help to find more novel therapeutic targets. Recent studies have shown that circular RNAs not only play an important role in the regulation of gene expression but also play an important role in the pathogenesis of cerebral ischemia.
OBJECTIVE: To review the regulatory role of circular RNAs in the pathogenesis of cerebral ischemia from the aspects of apoptosis, autophagy, oxidative stress, inflammation, angiogenesis, and blood-brain barrier, which is expected to provide ideas for clinical research on the role of circular RNAs in ischemic stroke.
METHODS: Relevant literatures published from March 2010 to March 2022 were retrieved in CNKI, WanFang Chinese database and PubMed using computer. Search terms included “ischemic stroke, acute ischemic stroke, RNA, ncRNA, RNA, Circular, circRNA, apoptosis, autophagy, oxidative stress, inflammation, angiogenesis, blood brain barrier” in Chinese and English. Finally 48 articles were included for further review.
RESULTS AND CONCLUSION: Circular RNAs are a class of non-coding RNA molecules with a closed loop structure, characterized by back splicing and lack of 5’ end cap and 3’ end polyadenylation tail. It exists widely in eukaryotic cells and has many important regulatory functions. Existing evidence has revealed that circular RNAs play an important role in the development of ischemic stroke. For example, circSHOC2 functions as a sponge for miR-7670-3p that can reduce neuronal damage by regulating autophagy-promoting sirt1 expression. A microarray study showed that the level of circHECTD1 was dramatically increased in mice after middle cerebral artery occlusion. Knockdown of circHECTD1 remarkably reduced cerebral infarct volume in mice, which in turn reduced neuronal damage and improved astrocyte activation. Circular RNAs are highly stable and evolutionarily conserved, and their circular structures are insensitive to ribonucleases and are more stable than linear ones, thus making circular RNAs more potential for developing novel disease diagnosis and treatment methods. At present, there is only a small amount of research on the mechanism of circular RNAs in ischemic stroke and its specific mechanism is still unclear. Related treatment strategies need to be further improved. Therefore, it is extremely necessary to further study the mechanism by which circular RNAs regulate ischemic stroke and to explore new potential targets for precise treatment of ischemic stroke in the future.
Key words: ischemic stroke, circular RNA, non-coding RNA, cerebral ischemia-reperfusion injury, apoptosis, autophagy, oxidative stress, review