Department of Neurovascular Centre, Changhai Hospital, Naval Medical University, Shanghai 200433, China; Department of Neurosurgery, Naval Medical Center, The PLA Naval Medical University, Shanghai 200052, China.
Department of Neurovascular Centre, Changhai Hospital, Naval Medical University, Shanghai 200433, China.
Biochim Biophys Acta Mol Basis Dis. 2024 Aug;1870(6):167278. doi: 10.1016/j.bbadis.2024.167278. Epub 2024 Jun 2.
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.
人类血管平滑肌细胞（hVSMCs）功能障碍与颅内动脉瘤（IAs）的发生发展密切相关。环状 RNA（circRNAs）通过抑制微小 RNA（miRNAs）的活性参与 IA 的发病机制。然而，hsa_circ_0008571 在 IAs 中的作用尚不清楚。
采用 circRNA 测序技术从人 IA 组织中鉴定 circRNAs。通过 Transwell、划痕愈合和细胞增殖实验来确定 circ_0008571 的功能。利用 CircInteractome 和 TargetScan 分析以及荧光素酶报告基因实验来鉴定 circ_0008571 的靶基因。此外，还进行了 circ_0008571 的敲低和过表达实验，以研究其在 IA 发展中的作用及其潜在的分子机制。
与颞浅动脉组织相比，IA 患者的血管壁中 hsa_circ_0008571 和整合素β 8（ITGB8）表达下调，而 miR-145-5p 的转录水平升高。在体外，hsa_circ_0008571 过表达后，细胞迁移和生长明显受到抑制。机制上，hsa_circ_0008571 通过直接海绵吸附作用抑制 miR-145-5p 的活性。此外，我们发现 ITGB8 表达和 TGF-β 介导的信号通路的激活显著增强。
hsa_circ_0008571-miR-145-5p-ITGB8 轴在 IA 进展中起重要作用。
