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

Zhaohui Li; Liang Han; Qianlei Liang; Zhehao Huang

doi:10.1016/j.brainresbull.2020.10.002

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

Brain Res Bull. 2021 Jan:166:1-11. doi: 10.1016/j.brainresbull.2020.10.002. Epub 2020 Oct 27.

Authors

Zhaohui Li¹, Liang Han², Qianlei Liang³, Zhehao Huang¹

Affiliations

¹ Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
² Department of Pathology, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China.
³ Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun 130033, Jilin, China. Electronic address: liangql@jlu.edu.cn.

PMID: 33127454
DOI: 10.1016/j.brainresbull.2020.10.002

Abstract

Background: 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.

Aims: The aim of this research is to explore the role of MEG3 in ICH.

Methods and results: 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.

Conclusions: 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.

Keywords: Brain microvascular endothelial cells; Intracerebral hemorrhage; Mllt1; lncRNA MEG3; miR-1930-5p.

Publication types

Retracted Publication