Long Non-Coding RNA MEG3 Promotes Apoptosis of Vascular Cells and is Associated with Poor Prognosis in Ischemic Stroke

Abstract

Aim: This study focused on the expression pattern of long non-coding RNA maternally expressed gene 3 (MEG3) and its value in ischemic stroke (IS). Methods:The expression pattern and the roles of MEG3 in the development of IS were explored in mice IS model and human brain microvascular endothelial cells (hBMECs). A case-control study, including 215 IS patients and 153 controls, was also conducted to investigate its prognostic value. Results:In vivo study showed that MEG3 increased significantly in the IS group (P 0.004), and its level remained stable within 3 to 48h after the onset of IS. Besides, the survival time of the mouse in the high MEG3 group was significantly lower than that in the low MEG3 group (P 0.042). In vitro study showed that oxygenglucose deprivation (OGD) treatment significantly up-regulated expressions of MEG3, Bax, and cleaved caspase-3, and further promoted apoptosis of hBMECs, while si-MEG3 blocked these effects. A human study showed that MEG3 increased markedly within 48h of IS onset and was positively associated with the National Institutes of Health Stroke Scale (r 0.347, P 0.001), modified Rankin Scale (r 0.385, P 0.001), high-sensitivity C-reactive protein (r 0.221, P 0.002) level, and infarct volume (r 0.201, P 0.006). Overall survival analysis showed that patients with higher MEG3 expression within 48h had a relatively poor prognosis (P 0.001). Meanwhile, multivariate analysis revealed that MEG3 was an independent prognostic marker for unfavorable functional outcome and death in IS patients. Conclusions: This study suggested that MEG3 might be considered as an intervention point and potential prognostic indicator for IS.after ischemic stroke by computed tomography (CT), and CT is mainly used to quickly eliminate intracranial tumors or cerebral hemorrhage 2) . (2) Magnetic resonance imaging (MRI) has higher sensitivity and specificity than CT, but most medical institutions in China cannot conduct MRI examinations 2) . (3) A recent systematic review suggested that the survival rate of IS patients who can receive thrombolytic therapy within 6h of symptom onset can be increased by 46.0%, and the disability rate caused by IS can be reduced by 42.1% 3) . Unfortunately, only about 2% of

Long Non-Coding RNA-Mediated Competing Endogenous RNA Networks in Ischemic Stroke: Molecular Mechanisms, Therapeutic Implications, and Challenges

“…Another case study was conducted to investigate the relationship between LncRNA MEG3 and prognostic value. MEG3 was upregulated in IS patients, positively associated with the NIHSS score, and negatively related to the prognosis of IS patients ( Wang M. et al, 2020 ). Thus, MEG3 is a potential marker for diagnosis and prognosis.…”

The Regulatory Functions of lncRNAs on Angiogenesis Following Ischemic Stroke

“…More importantly, the risk of death was higher in high MIAT expression group compared with the patients with low MIAT expression, in whom better prognosis and survival rate were observed (Zhu et al, 2018 ). In consistence with these findings, Wang et al ( 2020 ) also suggested that MEG3 expression was associated with poor prognosis in patients with ischemic stroke. The risk of death was increased in high MEG3 expression group compared with the control.…”

Comprehensive Analysis of Hub Genes Associated With Competing Endogenous RNA Networks in Stroke Using Bioinformatics Analysis

“…They were previously considered as “junk” in the mammal genome but now are found to function as a transcriptional regulator or post-transcriptional regulator: in the former, lncRNA combines with chromosomes and modifies the gene expression ( Ulitsky and Bartel, 2013 ), whereas in the latter, lncRNA can either directly impact the gene expression by regulating the degradation of genes or works as competing endogenous RNA (ceRNA) and sponge-specific miRNAs, thus indirectly regulating the gene expression ( Bao et al, 2018 ; Gong et al, 2020 ). Recently, aberrant expression of lncRNA has been reported to correlate with the onset, progression, and prognosis of acute ischemic stroke (AIS) ( Bai et al, 2014 ; Feng et al, 2019 ; Li et al, 2020a ; Wang et al, 2020a ; Fu et al, 2021 ); thus they are potential candidates for stroke diagnosis. Meanwhile, the mechanism of stroke involves a series of complicated processes, including energy depletion, ion imbalance, glutamate and free radical release, calcium channel dysfunction, inflammatory changes, and apoptosis ( Dirnagl et al, 1999 ).…”