基因敲除
小RNA
发病机制
癌症研究
细胞生长
下调和上调
血管平滑肌
环状RNA
表型
细胞迁移
细胞生物学
信号转导
体外
荧光素酶
生物
化学
分子生物学
基因
转染
免疫学
内分泌学
平滑肌
遗传学
作者
Zhiwen Lu,Shijie Zhu,Yina Wu,Xiaolong Xu,Siqi Li,Qinghai Huang
标识
DOI:10.1016/j.bbadis.2024.167278
摘要
The dysfunction of human vascular smooth cells (hVSMCs) is significantly connected to the development of intracranial aneurysms (IAs). By suppressing the activity of microRNAs (miRNAs), circular RNAs (circRNAs) participate in IA pathogenesis. Nevertheless, the role of hsa_circ_0008571 in IAs remains unclear. circRNA sequencing was used to identify circRNAs from human IA tissues. To determine the function of circ_0008571, Transwell, wound healing, and cell proliferation assays were conducted. To identify the target of circ_0008571, the analyses of CircInteractome and TargetScan, as well as the luciferase assay were carried out. Furthermore, circ_0008571 knockdown and over-expression were performed to investigate its functions in IA development and the underlying molecular mechanisms. Both hsa_circ_0008571 and Integrin beta 8 (ITGB8) were downregulated, while miR-145-5p transcription was elevated in the aneurysm wall of IAs patients compared to superficial temporal artery tissues. In vitro, cell migration and growth were dramatically suppressed after hsa_circ_0008571 overexpression. Mechanistically, has_circ_0008571 could suppress miR-145-5p activity by direct sponging. Moreover, we found that ITGB8 expression and the activation of the TGF-β-mediated signaling pathway were significantly enhanced. The hsa_circ_0008571-miR-145-5p-ITGB8 axis plays an essential role in IA progression.
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