Hu Teng, Li Di, Fan TiePing, Zhao XuSheng, Chen ZhongJun
Department of Neurological Intervention, Dalian Municipal Central Hospital, Dalian City, China.
Bioengineered. 2022 May;13(5):11564-11578. doi: 10.1080/21655979.2022.2068923.
Cerebral ischemia-reperfusion damages local brain tissue and impairs brain function, but its specific pathogenesis is still uncertain. Recent studies have clarified circPUM1 is aberrantly elevated in cerebral ischemia-reperfusion injury; however, circPUM1's function in cerebral ischemia-reperfusion-induced neuronal injury remains ambiguous. The results illustrated circPUM1 and DEAD-box helicase 5 were decreased, but microRNA-340-5p was elevated in transient middle cerebral artery occlusion mice and oxygen glucose deprivation/reoxygenation-treated SH-SY5Y cells. Knockdown of circPUM1 aggravated the neuronal injury in transient middle cerebral artery occlusion mice and motivated glial cell activation, neuronal apoptosis and inflammation. Enhancing circPUM1 restrained oxygen glucose deprivation/reoxygenation-induced SH-SY5Y cell apoptosis, the release of lactate dehydrogenase and inflammatory factors, and activation of nuclear factor-kappaB pathway, while elevating microRNA-340-5p aggravated oxygen glucose deprivation/reoxygenation-induced cell damage. Functional rescue experiments exhibited that the impacts of knockdown or enhancement of circPUM1 were turned around by microRNA-340-5p downregulation and DEAD-box helicase 5 silencing, respectively. Moreover, it was demonstrated that circPUM1 competitively adsorbed microRNA-340-5p to mediate DEAD-box helicase 5. All in all, this study clarifies that circPUM1 mitigates cerebral ischemia-reperfusion-induced neuronal injury by targeting the microRNA-340-5p/DEAD-box helicase 5 axis.
脑缺血再灌注会损伤局部脑组织并损害脑功能,但其具体发病机制仍不明确。最近的研究表明,circPUM1在脑缺血再灌注损伤中异常升高;然而,circPUM1在脑缺血再灌注诱导的神经元损伤中的作用仍不明确。结果表明,在短暂性大脑中动脉闭塞小鼠和氧糖剥夺/复氧处理的SH-SY5Y细胞中,circPUM1和DEAD盒解旋酶5减少,但微小RNA-340-5p升高。敲低circPUM1会加重短暂性大脑中动脉闭塞小鼠的神经元损伤,并促进胶质细胞活化、神经元凋亡和炎症。增强circPUM1可抑制氧糖剥夺/复氧诱导的SH-SY5Y细胞凋亡、乳酸脱氢酶和炎症因子的释放以及核因子-κB通路的激活,而升高微小RNA-340-5p则会加重氧糖剥夺/复氧诱导的细胞损伤。功能挽救实验表明,敲低或增强circPUM1的影响分别被微小RNA-340-5p下调和DEAD盒解旋酶5沉默所逆转。此外,研究表明circPUM1竞争性吸附微小RNA-340-5p以介导DEAD盒解旋酶5。总而言之,本研究阐明了circPUM1通过靶向微小RNA-340-5p/DEAD盒解旋酶5轴减轻脑缺血再灌注诱导的神经元损伤。