Department of Cardiovascular Surgery, Heart Center of Henan Provincial People's Hospital, Central China Fuwai Hospital, Central China Fuwai Hospital of Zhengzhou University, Zhengzhou, China.
Thorac Cancer. 2023 Aug;14(22):2158-2167. doi: 10.1111/1759-7714.15002. Epub 2023 Jun 20.
Vascular smooth muscle cells (VSMCs) are the predominant cell type of the aortic middle layer, the abnormal number or function of which has been demonstrated to have a role in thoracic aortic aneurysm (TAA). Here, this study aimed to identify the function of circ_0008285 in VSMC apoptosis.
Human VSMCs were treated with angiotensin II (Ang II) for functional experiments. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry were applied for function analysis. The interaction between miR-150-5p and circ_0008285 or brain acid-soluble protein 1 (BASP1) was also evaluated by dual-luciferase reporter assay and RNA immunoprecipitation assay. Exosomes were isolated by the commercial kit.
A highly expressed circ_0008285 was observed in the aortic tissues of TAA patients and Ang-II-induced VSMCs. Circ_0008285 deficiency dramatically reversed Ang-II-induced proliferation arrest and apoptosis promotion in VSMCs. Circ_0008285 functionally targeted miR-150-5p. MiR-150-5p inhibition attenuated the inhibitory effects of circ_0008285 silencing on Ang-II-evoked apoptosis in VSMCs. BASP1 was verified to be a target of miR-150-5p, and was proved to attenuate miR-150-5p-triggered apoptosis arrest in Ang-II-stimulated VSMCs. Additionally, extracellular circ_0008285 was packaged into exosomes, which could be transferred into the recipient cells.
Circ_0008285 silencing could suppress Ang-II-induced VSMCs apoptosis via miR-150-5p/BASP1 axis, adding further understanding of the pathogenesis of TAA.
血管平滑肌细胞(VSMCs)是主动脉中层的主要细胞类型,其数量或功能异常已被证明在胸主动脉瘤(TAA)中起作用。本研究旨在鉴定 circ_0008285 在 VSMC 凋亡中的作用。
用血管紧张素 II(Ang II)处理人 VSMCs 进行功能实验。应用细胞计数试剂盒-8、5-乙炔基-2'-脱氧尿苷(EdU)和流式细胞术进行功能分析。还通过双荧光素酶报告基因检测和 RNA 免疫沉淀检测评估了 circ_0008285 与 miR-150-5p 或脑酸性可溶性蛋白 1(BASP1)之间的相互作用。通过商业试剂盒分离外泌体。
在 TAA 患者的主动脉组织和 Ang-II 诱导的 VSMCs 中观察到高表达的 circ_0008285。circ_0008285 缺乏可显著逆转 Ang-II 诱导的 VSMCs 增殖停滞和凋亡促进作用。circ_0008285 功能性靶向 miR-150-5p。抑制 miR-150-5p 可减弱 circ_0008285 沉默对 Ang-II 诱导的 VSMCs 凋亡的抑制作用。BASP1 被验证为 miR-150-5p 的靶标,并被证明可减弱 Ang-II 刺激的 VSMCs 中 miR-150-5p 触发的凋亡阻滞。此外,细胞外 circ_0008285 被包装到外泌体中,并可转移到受体细胞中。
circ_0008285 沉默可通过 miR-150-5p/BASP1 轴抑制 Ang-II 诱导的 VSMCs 凋亡,进一步了解 TAA 的发病机制。