Li Shenghua, Qu Xiang, Qin Zhenxiu, Gao Jinggui, Li Jinpin, Liu Jingli
Department of Neurology, Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Mol Neurobiol. 2023 May;60(5):2767-2785. doi: 10.1007/s12035-023-03216-y. Epub 2023 Jan 30.
miR-212-5p has been reported to be involved in many biological processes. However, the role of miR-212-5p in ischemic stroke remains unclear. This study explored the biological role and potential mechanism of miR-212-5p in ischemic stroke by investigating the lncfos/miR-212-5p/CASP7 axis. A total of 32 patients with ischemic stroke and 32 age- and sex-matched healthy controls (HCs) were enrolled in this study. In addition, 336 rats were used in this study. The rats were subjected to middle cerebral artery occlusion (MCAO) and intracerebroventricular injection of a microRNA (miRNA) agomir, a miRNA antagomir, a short hairpin RNA (shRNA) lentiviral vector, or a negative control. The neurological deficit score was calculated; the infarct volume was measured; histopathological assays were performed; the neuronal apoptosis rate was determined; and the lncfos, miR-212-5p, and CASP7 expression levels in the peri-infarct area were assessed. In this study, we found that the expression level of miR-212-5p was significantly downregulated in the peri-infarct area and blood of the MCAO model rats and the blood of patients with ischemic stroke. A double-luciferase experiment showed that CASP7 was a direct target gene of miR-212-5p and that miR-212-5p was a target miRNA of lncfos. Lateral ventricular injection of the miR-212-5p agomir effectively inhibited the apoptosis induced by ischemic brain damage, reduced the infarct volume, attenuated the neurological deficit symptoms, and downregulated the expression of CASP7 in the peri-infarct area of the MCAO model rats. Suppressing lncfos with sh-fos led to the upregulated expression of miR-212-5p and played a neuroprotective role in the rat MCAO models. We concluded that miR-212-5p plays a neuroprotective role in ischemic stroke and that its function is regulated by the lncfos/miR-212-5p/CASP7 axis. Moreover, miR-212-5p may be a potential biomarker and therapeutic target for ischemic stroke.
据报道，miR-212-5p参与多种生物学过程。然而，miR-212-5p在缺血性卒中中的作用仍不清楚。本研究通过研究lncfos/miR-212-5p/CASP7轴，探讨miR-212-5p在缺血性卒中中的生物学作用及潜在机制。本研究共纳入32例缺血性卒中患者和32例年龄、性别匹配的健康对照（HCs）。此外，本研究使用了336只大鼠。对大鼠进行大脑中动脉闭塞（MCAO），并向脑室内注射微小RNA（miRNA）激动剂、miRNA拮抗剂、短发夹RNA（shRNA）慢病毒载体或阴性对照。计算神经功能缺损评分；测量梗死体积；进行组织病理学检测；测定神经元凋亡率；评估梗死周边区lncfos、miR-212-5p和CASP7的表达水平。在本研究中，我们发现miR-212-5p在MCAO模型大鼠梗死周边区和血液以及缺血性卒中患者血液中的表达水平显著下调。双荧光素酶实验表明，CASP7是miR-212-5p的直接靶基因，且miR-212-5p是lncfos的靶miRNA。侧脑室注射miR-212-5p激动剂可有效抑制缺血性脑损伤诱导的细胞凋亡，减小梗死体积，减轻神经功能缺损症状，并下调MCAO模型大鼠梗死周边区CASP7的表达。用sh-fos抑制lncfos可导致miR-212-5p表达上调，并在大鼠MCAO模型中发挥神经保护作用。我们得出结论，miR-212-5p在缺血性卒中中发挥神经保护作用，其功能受lncfos/miR-212-5p/CASP7轴调控。此外，miR-212-5p可能是缺血性卒中的潜在生物标志物和治疗靶点。
