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. 2020 Aug;43(4):1337-1350.
doi: 10.1007/s10753-020-01212-1.

lncRNA ZFAS1 Improves Neuronal Injury and Inhibits Inflammation, Oxidative Stress, and Apoptosis by Sponging miR-582 and Upregulating NOS3 Expression in Cerebral Ischemia/Reperfusion Injury

Yanyan Zhang  1 , Yiping Zhang  2
Affiliations

lncRNA ZFAS1 Improves Neuronal Injury and Inhibits Inflammation, Oxidative Stress, and Apoptosis by Sponging miR-582 and Upregulating NOS3 Expression in Cerebral Ischemia/Reperfusion Injury

Yanyan Zhang et al. Inflammation. 2020 Aug.

Abstract

The interplay between lncRNAs and miRNAs was reported to be associated with cerebral ischemia reperfusion injury (CIRI). Besides, the lncRNA ZFAS1 was significantly downregulated in patients with ischemic stroke. However, the exact biological role of ZFAS1 and its mechanism in CIRI remain to be elucidated. The current study was designed to explore the protective effects of ZFAS1 on neuronal injury, inflammation, oxidative stress, and neuronal apoptosis in CIRI. ZFAS1 and miR-582-3p levels were assessed by RT-qPCR. Cerebral infarction was assessed by tetrazolium chloride (TTC) staining. Inflammation and oxidative stress were measured by ELISA and matched test kits. The apoptotic rate and apoptotic mediators in OGD/R-suffered PC12 cells were respectively detected by flow cytometry and western blot. NO production was measured by NO kit and western blot assay. The regulatory relationship between lncRNA ZFAS1 and miR-582-3p was analyzed using the luciferase reporter assay. ZFAS1 was downregulated in CIRI. ZFAS1 overexpression alleviated neurological function deficit and neuronal damage in a MCAO rat model. Besides, ZFAS1 upregulation or miR-582-3p downregulation could both inhibit the inflammation, oxidative stress, and apoptosis and enhance NO level in OGD/R-suffered PC12 cells. Reporter assay indicated that ZFAS1 served as a molecular sponge for miR-582-3p. In addition, ZFAS1 could negatively regulate miR-582-3p expression and release its effects in CIRI. Taken together, our study revealed that lncRNA ZFAS1 protected against neuronal damage and modulated the inflammation, oxidative stress, apoptosis, and NO level via regulating miR-582-3p in cerebral I/R injury. Therefore, lncRNA ZFAS1 might serve as a therapeutic application to suppress CIRI progression.

Keywords: NOS3; cerebral ischemia reperfusion injury; lncRNA-ZFAS1; miR-582.

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