Circular RNA CCDC66 facilitates abdominal aortic aneurysm through the overexpression of CCDC66

Abstract

Funding information The fifth group of bosom friends and talents plan of Hanyang District, Wuhan 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. Significance of the study: It was firstly displayed in our study that depletion of circCCDC66 induced proliferation augmentation and apoptosis reduction of vascular smooth muscle cells (VSMCs). Meanwhile, circCCDC66/miR-342-3p/CCDC66 axis was proved can play the function of modulating the cell proliferation and apoptosis of VSMCs, which provided us a novel molecular mechanism in AAA.

Circular RNAs as Competing Endogenous RNAs in Cardiovascular and Cerebrovascular Diseases: Molecular Mechanisms and Clinical Implications

“…circCBFB facilitates VSMC proliferation and inhibits VSMC apoptosis via the circCBFB/miR-28-5p/GRIA4/LYPD3 axis ( 58 ). circCCDC66 sponges miR-342-3p to upregulate its host gene CCDC66 in VSMCs and regulates VSMC apoptosis and proliferation ( 59 ). These newly identified mechanisms may provide novel options for the treatment of aneurysm.…”

Circular RNA Expression: Its Potential Regulation and Function in Abdominal Aortic Aneurysms

“…In line with the above results, Wang et al examined the competitive endogenous RNA (ceRNA) mechanism related to certain apoptotic circRNAs. For instance, two miRNAs (mmu-let-7a-2-3p and mmu-miR-199a-3p) of differentially expressed mmu_circRNA_001265 and their response elements were Oxidative Medicine and Cellular Longevity To prove the role of circRNA CCDC66 in the pathogenesis of AAAs and identify its corresponding pathway, Yang et al carried out a study and found that circCCDC66 played a role in the proliferation of VSMCs [91]. Through further investigation, they discovered that circCCDC66 promoted the expression of CCDC66, and CCDC66 suppression had the same effect as circCCDC66 deletion on the development and apoptosis of VSMCs.…”

“…To prove the role of circRNA CCDC66 in the pathogenesis of AAAs and identify its corresponding pathway, Yang et al carried out a study and found that circCCDC66 played a role in the proliferation of VSMCs [ 91 ]. Through further investigation, they discovered that circCCDC66 promoted the expression of CCDC66, and CCDC66 suppression had the same effect as circCCDC66 deletion on the development and apoptosis of VSMCs.…”

Circ-CCDC66 upregulates REXO1 expression to aggravate cervical cancer progression via restraining miR-452-5p

“…In the past decades, the functions of circRNAs in multiple biological progressions have been deeply studied, including cervical cancer [8][9][10][11][12]. Gao [17][18][19][20]. However, the role circ-CCDC66 in cervical cancer development is still uncovered.…”