RETRACTED: Long noncoding RNA MEG3 contributes to dysfunction of brain microvascular endothelial cells after intracerebral hemorrhage by regulating the miR-1930-5p/Mllt1 axis

Abstract

Intracerebral hemorrhage (ICH) is a subtype of stroke and causes disability and death worldwide. The roles of long noncoding RNAs (lncRNAs) in brain function and neurological diseases have been revealed. LncRNA maternally expressed gene 3 (MEG3) is involved in neurological impairment, but its role in ICH remains unknown. The aim of this research is to explore the role of MEG3 in ICH. Here, we established an ICH mouse model via intracerebral injection of autologous blood. Primary brain microvascular endothelial cells (BMECs) were treated with oxygen-and-glucose-deprivation (OGD) plus hemin to establish the model in vitro. We observed that MEG3 expression was significantly upregulated in both ICH mouse model and OGD/hemin (OGD/H) induced BMECs. The downregulation of MEG3 suppressed cell apoptosis and the activation of NOD-like receptor family protein 3 (NLRP3) inflammasome in OGD/H-induced BMECs. In ICH mice, MEG3 downregulation inhibited cell apoptosis and improved brain dysfunction. Mechanistically, MEG3 was confirmed to act as a molecular sponge for microRNA (miR)-1930-5p, and Mllt1 was a downstream target for miR-1930-5p. MEG3 competitively bound with miR-1930-5p to upregulate Mllt1. We further verified that Mllt1 overexpression reversed the inhibitory effect of miR-1930-5p in OGD/H-induced BMECs. In conclusion, lncRNA MEG3 promoted the dysfunction of BMECs by modulating the miR-1930-5p/Mllt1 axis, which provides a potential target in gene therapy for brain injury following ICH.