Long noncoding MIAT acting as a ceRNA to sponge microRNA-204-5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1
Long noncoding MIAT acting as a ceRNA to sponge microRNA-204-5p to participate in cerebral microvascular endothelial cell injury after cerebral ischemia through regulating HMGB1
复制标题
长非编码MIAT作为ceRNA海绵microRNA-204-5p通过调节HMGB1参与脑缺血后脑微血管内皮细胞损伤
DOI：
10.1002/jcp.29334
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发表时间：
2019-10-19
影响因子：
5.6
通讯作者：
Teng, Junfang
中科院分区：
文献类型：
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作者：
Deng, Wenjing;Fan, Chenghe;Teng, Junfang
本研究旨在探讨心肌梗死相关长链非编码RNA转录本（MIAT's）作为竞争性内源性RNA（ceRNA）海绵microRNA-204- 5 p（miR-204- 5 p）对脑缺血损伤后脑微血管内皮细胞（CMEC）高迁移率族蛋白1（HMGB 1）表达的调控作用。采用线栓法建立大鼠大脑中动脉闭塞（MCAO）脑缺血模型，分别注射空质粒和MIAT siRNA质粒。采用原代培养的大鼠CMECs，通过氧糖剥夺（OGD）建立体外脑缺血损伤模型。用空质粒和MIAT siRNA质粒转染细胞。探讨MIAT/miR-204- 5 p/HMGB 1轴在CMECs损伤和血管生成中的作用。测定MIAT与miR-204- 5 p沿着miR-204 - 5 p与HMGB 1之间的结合位点。MIAT在MCAO大鼠脑组织中过表达，抑制MIAT可减轻MCAO大鼠脑组织的损伤。抑制MIAT可促进MCAO大鼠脑组织血管生成，促进miR-204- 5 p表达，抑制HMGB 1表达。抑制MIAT可减少CMEC损伤，诱导CMEC血管生成，增加存活神经元数量，促进miR-204- 5 p表达，抑制OGD处理的CMEC中HMGB 1表达。MIAT通过与miR-204- 5 p竞争性结合促进HMGB 1表达，调节脑缺血后CMECs的损伤。我们的研究表明，MIAT通过竞争性结合miR-204- 5 p促进HMGB 1的表达，从而调节脑缺血后CMECs的损伤。
This study is applied to the investigation of the long noncoding RNA myocardial infarction associated transcript's (MIAT's) role in regulating the expression of high-mobility group box 1 (HMGB1) in cerebral microvascular endothelial cell (CMEC) injury after cerebral ischemia by serving as a competitive endogenous RNA (ceRNA) to sponge microRNA-204-5p (miR-204-5p). The cerebral ischemia model of middle cerebral artery occlusion (MCAO) in rats was established by the suture method, in which rats were injected with empty plasmids and MIAT siRNA plasmids. The cerebral ischemia injury model in vitro was established through oxygen glucose deprivation (OGD) in primary cultured CMECs in rats. The cells were transfected with empty plasmids and MIAT siRNA plasmids. The MIAT/miR-204-5p/HMGB1 axis' function in damage and angiogenesis of CMECs were explored. The binding site between MIAT and miR-204-5p along with that between miR-204-5p and HMGB1 was determined. MIAT was overexpressed in MCAO rats' brain tissue and inhibited MIAT attenuated the injury of brain tissue in MCAO rats. Inhibition of MIAT promoted angiogenesis, promoted miR-204-5p expression and inhibited HMGB1 expression in brain tissue of MCAO rats. Inhibition of MIAT reduced CMEC damage, induced angiogenesis of CMECs, increased the number of surviving neurons, promoted miR-204-5p expression and inhibited HMGB1 expression in CMECs treated with OGD. MIAT promoted HMGB1 expression by competitive binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia. Our study showed that MIAT promoted HMGB1 expression by competitively binding to miR-204-5p to regulate the injury of CMECs after cerebral ischemia.