Med Sci Monit. 2021 Jul 16;27:e929435.doi: 10.12659/MSM.929435.

lncRNA MEG3 Downregulation Relieves Intracerebral Hemorrhage by Inhibiting Oxidative Stress and Inflammation in an miR-181b-Dependent Manner

Bo Xie  1 Mingliang Qiao  1 Jialong Xuan  2 Affiliations

Free PMC article

Abstract

BACKGROUND This study was designed to illustrate the effects and latent mechanism of lncRNA maternally expressed gene 3 (MEG3) on intracerebral hemorrhage (ICH)-induced brain injury. MATERIAL AND METHODS An ICH rat model was generated to determine the role of lncRNA MEG3 in ICH. The interaction between lncRNA MEG3 and microRNA (miR)-181b were confirmed by Starbase and dual-luciferase reporter assay. One hour (h) or 3 days after ICH stimulation, rat neurological injury was evaluated by modified Neurological Severity Score (mNSS). Brain water content and cell apoptosis were assessed using brain edema assessment and flow cytometry (FCM), respectively. Caspase3 activity was also determined. Enzyme-linked immunosorbent assay (ELISA) was applied to evaluate the levels of pro-inflammatory cytokines. Moreover, the representative biomarkers of oxidative stress were evidenced using detection kits. RESULTS The lncRNA MEG3 level in ICH rat brain tissues was higher than that in the sham group. miR-181b was a direct target of lncRNA MEG3 and it was downregulated in brain tissues of ICH rats. Notably, we found that neurobehavioral scores, brain water content, and neuronal apoptosis were decreased and caspase3 activity was reduced in MEG3-shRNA-treated ICH rats, while we observed the opposite result in ICH+MEG3-shRNA+miR-181b inhibitor rats. Further analyses revealed that MEG3-shRNA inhibited inflammatory cytokines release and reduced oxidative stress. All these results were reversed by miR-181b inhibitor. In addition, MEG3-shRNA activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway, which was reversed by miR-181b inhibitor. CONCLUSIONS MEG3-shRNA restrained oxidative stress and inflammation following ICH in an miR-181b-dependent manner.

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