CircRNA_0003307 promoted brain microvascular endothelial cell angiogenesis, invasion, and migration in cerebral ischemia-reperfusion injury: Potential involvement of miRNA-191-5p/CDK6 pathway

IF 2.9 3区 医学 Q2 NEUROSCIENCES Neuroscience Pub Date : 2024-09-14 DOI:10.1016/j.neuroscience.2024.09.025
Ying Wu , Zhi Zheng , Xue Bai , Ping Liu , Shanshan Hu , Lingxue Wang , Sijing Yang
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Abstract

Backgrounds

The role of miR-191-5p in cerebral ischemia–reperfusion (I/R) injury has been established, with its expression in endothelial cells demonstrating anti-angiogenic effects. A potential circular RNA, circRNA_0003307, has been identified through bioinformatics analysis as a candidate for interaction with miR-191-5p, yet its functional significance in brain I/R injury remains unexplored. We aimed to investigate whether circRNA_0003307 regulates brain microvascular endothelial cell (BMEC) vascular tube formation, invasion, and migration by regulating the miR-191-5p cascade.

Methods

Mouse BMECs (bEnd.3) were cultured and exposed to oxygen-glucose deprivation (OGD). The effects of circRNA_0003307 on vessel-like tube formation and cellular migration were examined. In addition, we investigated the protective effects of circRNA_0003307 on I/R injury in mice.

Results

The results showed the level of circRNA_0003307 was concentration-dependently increased in OGD-induced bEnd.3 cells. ODG-induction enhanced angiogenesis, migration, and invasion of bEnd.3 cells, which were further promoted by the transfection of pcDNA-0003307. Silencing circRNA_0003307 expression showed the opposite results. The dual luciferase assay demonstrated miRNA-191-5p interacted with circRNA_00033073′ UTR, and miRNA-191-5p could bind with CDK6. Meanwhile, circRNA_0003307 promoted the expression of CDK6 by sponging miRNA-191-5p. The overexpression of circRNA_0003307 activated the angiogenesis, migration, and invasion of OGD-induced bEnd.3 cells, which were hindered by miRNA-191-5p mimic or siRNA-CDK6. Thus, circRNA_0003307 promoted ODG-induced angiogenesis, migration, and invasion of bEnd.3 cells by targeting miR-191-5p/CDK6 axis. In vivo, circRNA_0003307 had protective effects on brain I/R injury, including neuroprotection, anti-apoptosis and angiogenesis.

Conclusion

CircRNA_0003307 may be a promising therapeutic target for the treatment of cerebral I/R injury.
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CircRNA_0003307促进脑缺血再灌注损伤中脑微血管内皮细胞的血管生成、侵袭和迁移miRNA-191-5p/CDK6 通路的潜在参与运行标题:circRNA_0003307在脑缺血再灌注损伤中的功能:miRNA-191-5p/CDK6通路的潜在参与
背景:miR-191-5p在脑缺血再灌注(I/R)损伤中的作用已被证实,它在内皮细胞中的表达具有抗血管生成的作用。通过生物信息学分析,一种潜在的环状 RNA--circRNA_0003307--已被确定为与 miR-191-5p 相互作用的候选者,但其在脑 I/R 损伤中的功能意义仍有待探索。我们旨在研究circRNA_0003307是否通过调节miR-191-5p级联来调控脑微血管内皮细胞(BMEC)血管管的形成、侵袭和迁移:方法:培养小鼠脑微血管内皮细胞(bEnd.3)并将其暴露于氧气-葡萄糖剥夺(OGD)条件下。研究了circRNA_0003307对血管样管形成和细胞迁移的影响。此外,我们还研究了 circRNA_0003307 对小鼠 I/R 损伤的保护作用:结果:结果表明,circRNA_0003307的水平在ODG诱导的bEnd.3细胞中呈浓度依赖性增加。ODG诱导增强了bEnd.3细胞的血管生成、迁移和侵袭,转染pcDNA-0003307进一步促进了血管生成、迁移和侵袭。抑制 circRNA_0003307 的表达则会产生相反的结果。双荧光素酶试验表明,miRNA-191-5p与circRNA_00033073'UTR相互作用,miRNA-191-5p能与CDK6结合。同时,circRNA_0003307通过疏导miRNA-191-5p促进CDK6的表达。circRNA_0003307的过表达激活了OGD诱导的bEnd.3细胞的血管生成、迁移和侵袭,而miRNA-191-5p模拟物或siRNA-CDK6则阻碍了血管生成、迁移和侵袭。因此,circRNA_0003307通过靶向miR-191-5p/CDK6轴促进了ODG诱导的bEnd.3细胞的血管生成、迁移和侵袭。在体内,circRNA_0003307对脑I/R损伤具有保护作用,包括神经保护、抗凋亡和血管生成:结论:CircRNA_0003307可能是治疗脑I/R损伤的一个很有前景的治疗靶点。
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来源期刊
Neuroscience
Neuroscience 医学-神经科学
CiteScore
6.20
自引率
0.00%
发文量
394
审稿时长
52 days
期刊介绍: Neuroscience publishes papers describing the results of original research on any aspect of the scientific study of the nervous system. Any paper, however short, will be considered for publication provided that it reports significant, new and carefully confirmed findings with full experimental details.
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