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 oxygen–glucose 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.