Abdominal aortic aneurysm (AAA) is fatal meanwhile unpredictable asymptomatic cardiovascular disease. Available data suggests the potential participation of circular RNAs (circRNAs) in AAA pathogenesis. But direct evidence is limited. The present study is to functionally and mechanically characterize circRNA CCDC66 (circCCDC66) in AAA. Previous work indicated the differentially expressed circCCDC66 in AAA. At molecular level, circCCDC66, miR‐342‐3p and CCDC66 transcript were measured through real‐time quantitative polymerase chain reaction assay. Functionally, we examined the cellular behaviours of circCCDC66‐depleted or CCDC66‐depleted vascular smooth muscle cells (VSMCs) including proliferation and apoptosis. It elucidated that depletion of circCCDC66 induced proliferation facilitation and apoptosis reduction. Mechanically, we addressed the interplay among circCCDC66, miR‐342‐3p and CCDC66 transcript using RNA immunoprecipitation, RNA pull‐down and luciferase reporter experiments. Through mechanical validation, we discovered the positive regulation of circCCDC66 on its host gene CCDC66. Loss of CCDC66 mimicked the effects of circCCDC66 silencing on VSMC growth. Moreover, it uncovered that circCCDC66 regulated CCDC66‐dependent VSMC growth through sponging miR‐342‐3p. Rescue experiments aimed to address the functional role of regulatory network formed by circCCDC66, miR‐342‐3p and CCDC66 in VSMC growth and apoptosis. Suppressing miR‐342‐3p or overexpressing CCDC66 could reverse VSMC growth caused by circCCDC66 deficiency. Our study further emphasized and first unveiled the function of circCCDC66 in VSMC proliferation. CircCCDC66 upregulated its host gene through its role of miR‐342‐3p sponge, and hinted a novel molecular mechanism in AAA.

中文翻译：

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环状RNA CCDC66通过CCDC66的过表达促进腹主动脉瘤。

腹主动脉瘤（AAA）是致命的，同时不可预测的无症状心血管疾病。现有数据表明环状RNA（circRNA）可能参与AAA发病机制。但是直接的证据是有限的。本研究旨在功能和机械表征AAA中的circRNA CCDC66（circCCDC66）。先前的工作表明在AAA中差异表达circCCDC66。在分子水平上，通过实时定量聚合酶链反应测定法测量了circCCDC66，miR-342-3p和CCDC66转录本。在功能上，我们检查了circCCDC66耗尽或CCDC66耗尽的血管平滑肌细胞（VSMC）的细胞行为，包括增殖和凋亡。这说明circCCDC66的耗竭诱导增殖促进和凋亡减少。机械上 我们使用RNA免疫沉淀，RNA下拉和荧光素酶报告基因实验解决了circCCDC66，miR-3342-3p和CCDC66转录本之间的相互作用。通过机械验证，我们发现了circCCDC66对宿主基因CCDC66的正调控。CCDC66的丢失模拟了circCCDC66沉默对VSMC生长的影响。此外，它发现circCCDC66通过使miR-342-3p变海绵来调节依赖CCDC66的VSMC的生长。救援实验旨在解决circCCDC66，miR-342-3p和CCDC66形成的调控网络在VSMC生长和凋亡中的功能。抑制miR-3342p或过表达CCDC66可以逆转circCCDC66缺乏引起的VSMC生长。我们的研究进一步强调并首先揭示了circCCDC66在VSMC增殖中的功能。