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.

中文翻译：

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长链非编码RNA MEG3通过调节miR-1930-5p/Mllt1轴导致脑出血后脑微血管内皮细胞功能障碍

背景

脑出血 (ICH) 是中风的一种亚型，在全球范围内导致残疾和死亡。长链非编码 RNA (lncRNA) 在脑功能和神经系统疾病中的作用已被揭示。LncRNA 母源表达基因 3 (MEG3) 与神经功能障碍有关，但其在 ICH 中的作用尚不清楚。

宗旨

本研究的目的是探讨 MEG3 在 ICH 中的作用。

方法和结果

在这里，我们通过脑内注射自体血建立了 ICH 小鼠模型。用氧和葡萄糖剥夺（OGD）加氯化血红素处理原代脑微血管内皮细胞（BMECs）以建立体外模型. 我们观察到 MEG3 表达在 ICH 小鼠模型和 OGD/hemin (OGD/H) 诱导的 BMEC 中均显着上调。MEG3 的下调抑制了 OGD/H 诱导的 BMEC 中的细胞凋亡和 NOD 样受体家族蛋白 3（NLRP3）炎性体的激活。在 ICH 小鼠中，MEG3 下调抑制细胞凋亡并改善脑功能障碍。从机制上讲，MEG3 被证实充当 microRNA (miR)-1930-5p 的分子海绵，而 Mllt1 是 miR-1930-5p 的下游靶标。MEG3 与 miR-1930-5p 竞争性结合以上调 Mllt1。我们进一步证实，Mllt1 过表达逆转了 miR-1930-5p 在 OGD/H 诱导的 BMEC 中的抑制作用。

结论

总之，lncRNA MEG3通过调节miR-1930-5p/Mllt1轴促进了BMECs的功能障碍，这为ICH后脑损伤的基因治疗提供了潜在的靶点。