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微小RNA-6760-5p通过靶向Yes相关蛋白1抑制烟雾病间接血运重建患者的新生血管形成。

miR-6760-5p suppresses neoangiogenesis by targeting Yes-associated protein 1 in patients with moyamoya disease undergoing indirect revascularization.

作者信息

Wen Yunyu, Chen Junda, Long Tinghan, Chen Fangzhou, Wang Zhibin, Chen Siyuan, Zhang Guozhong, Li Mingzhou, Zhang Shichao, Kang Huibin, Feng Wenfeng, Wang Gang

机构信息

Neurosurgery Department, Nanfang Hospital, Southern Medical University, Located in Guangzhou, Guangdong, China; The Laboratory for Precision Neurosurgery is affiliated with Nanfang Hospital at Southern Medical University, Located in Guangzhou, Guangdong, China; The Institute of Brain Disease is part of Nanfang Hospital at Southern Medical University, Located in Guangzhou, Guangdong, China.

Neurosurgery Department, Nanfang Hospital, Southern Medical University, Located in Guangzhou, Guangdong, China; The Laboratory for Precision Neurosurgery is affiliated with Nanfang Hospital at Southern Medical University, Located in Guangzhou, Guangdong, China.

出版信息

Gene. 2025 Feb 10;937:149152. doi: 10.1016/j.gene.2024.149152. Epub 2024 Dec 9.

Abstract

OBJECTIVE

The aim of this research was to investigate the specific regulatory role of miR-6760-5p in angiogenesis in moyamoya disease.

METHODS

HUVECs were transfected with miR-6760-5p inhibitor and mimics fragments, then subjected to assays for cell proliferation, migration, and tube formation. Subsequently, downstream target genes of miR-6760-5p were predicted and the protein expression levels of these genes were evaluated. The presence of miR-6760-5p and YAP1 was verified by a dual luciferase reporter gene test, followed by an assessment of the effects of YAP1 and miR-6760-5p on the HUVECs.

RESULTS

Comparatively to the control group, increased expression of miR-6760-5p decreased cell growth, movement, and tube formation. YAP1 gene was discovered as a target controlled by miR-6760-5p, with subsequent investigation confirming YAP1 as a gene regulated by miR-6760-5p. Additionally, miR-6760-5p was found to counteract the angiogenesis-promoting effect of YAP1.

CONCLUSION

The results of this research suggest a possible link between the miR-6760-5p gene found in the cerebrospinal fluid of individuals with moyamoya disease and the process of vascularization in this particular condition. The findings indicate that miR-6760-5p may be a new molecular indicator and potential target for the diagnosis of moyamoya disease.

摘要

目的

本研究旨在探讨miR-6760-5p在烟雾病血管生成中的具体调控作用。

方法

将miR-6760-5p抑制剂和模拟片段转染到人脐静脉内皮细胞(HUVECs),然后进行细胞增殖、迁移和管形成检测。随后,预测miR-6760-5p的下游靶基因,并评估这些基因的蛋白表达水平。通过双荧光素酶报告基因试验验证miR-6760-5p和YAP1的存在,接着评估YAP1和miR-6760-5p对HUVECs的影响。

结果

与对照组相比,miR-6760-5p表达增加会降低细胞生长、运动和管形成。发现YAP1基因是受miR-6760-5p调控的靶标,后续研究证实YAP1是受miR-6760-5p调控的基因。此外,发现miR-6760-5p可抵消YAP1的促血管生成作用。

结论

本研究结果表明,在烟雾病患者脑脊液中发现的miR-6760-5p基因与这种特定疾病状态下的血管形成过程之间可能存在联系。研究结果表明,miR-6760-5p可能是烟雾病诊断的新分子指标和潜在靶点。

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