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

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/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.

lncRNA MEG3 aggravated neuropathic pain and astrocyte overaction through mediating miR-130a-5p/CXCL12/CXCR4 axis

“…Similarly, MEG3 is up-regulated in the brain tissue of intracerebral hemorrhage (ICH) rats. Abating MEG3 expression restrains edema, neuronal apoptosis, and the release of inflammatory cytokines and oxidative stress in the brain tissue of ICH rats [ 18 ]. Therefore, MEG3 can play a role in neuroinflammation.…”

Long non-coding RNA MEG3 promotes tumor necrosis factor-alpha induced oxidative stress and apoptosis in interstitial cells of cajal via targeting the microRNA-21 /I-kappa-B-kinase beta axis

“…MEG3 has been identified as a tumor inhibitor and can also promote inflammation, oxidative stress, and cell apoptosis of non-tumor cells in previous studies [ 12 , 16 , 17 ]. As shown in Figure 2(a) , the MEG3 expression was significantly elevated by TNF-α treatment in ICC ( p < 0.05), which suggested that MEG3 might be involved in the stress process of ICC with TNF-α stimulation.…”

“…Many previous studies have demonstrated that MEG3 participates in the inflammation progression and apoptosis in different types of non-cancer cell [ 15 , 50 , 51 ]. A study by Xie B et al suggested that MEG3 downregulation suppresses the inflammation cytokines and oxidative stress level [ 17 ]. In agreement with these reporters, our study verified MEG3 was upregulated by TNF-α in ICC, and knockdown of MEG3 reduced inflammation, oxidative stress, and apoptosis in TNF-α-treated ICC.…”

Epigenetic mechanisms and potential therapeutic targets in stroke

“…129,134,135 In an ICH rat model, MEG3 downregulation reduced caspase-3 activity and apoptosis, and ameliorated inflammation and oxidative stress. 136 Expression of MEG3 was increased in the cerebrospinal fluid of SAH patients, and in the blood of ischemic stroke patients, which was associated with the severity of post-stroke brain damage. 137,138 These clinical studies further indicate that MEG3 may be involved in exacerbation of brain injury after stroke.…”