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

J Atheroscler Thromb. 2020 Jul 1;27(7):718-726. doi: 10.5551/jat.50674. Epub 2019 Oct 25.

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.

Keywords: Ischemic stroke; Long non-coding RNA; Maternally expressed gene 3; Prognosis.

MeSH terms

  • Aged
  • Animals
  • Apoptosis / genetics
  • Apoptosis Regulatory Proteins / analysis
  • Apoptosis Regulatory Proteins / genetics
  • Case-Control Studies
  • China / epidemiology
  • Disease Models, Animal
  • Female
  • Functional Status
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Ischemic Stroke* / complications
  • Ischemic Stroke* / diagnosis
  • Ischemic Stroke* / genetics
  • Ischemic Stroke* / mortality
  • Male
  • Predictive Value of Tests
  • Prognosis
  • RNA, Long Noncoding* / analysis
  • RNA, Long Noncoding* / genetics
  • Severity of Illness Index

Substances

  • Apoptosis Regulatory Proteins
  • MEG3 non-coding RNA, human
  • MEG3 non-coding RNA, mouse
  • RNA, Long Noncoding