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Circ_0002331 Interacts with ELAVL1 to Improve ox-LDL-Induced Vascular Endothelial Cell Dysfunction via Regulating
1Department of Cardiovascular Medicine, Lishui People's Hospital, Lishui, Zhejiang, China.
Insights
Circular RNA circ_0002331 is downregulated in atherosclerosis (AS). Restoring circ_0002331 protects against ox-LDL induced dysfunction in human umbilical vein endothelial cells (HUVECs) by regulating CCND2.
Area of Science:
- Molecular Biology
- Cardiovascular Research
Background:
- Circular RNAs (circRNAs) are emerging regulators in atherosclerosis (AS).
- The specific role and mechanism of circ_0002331 in AS remain largely unexplored.
- Understanding circRNA functions is crucial for developing novel AS therapies.
Purpose of the Study:
- To investigate the function and mechanism of circ_0002331 in the context of AS.
- To elucidate the regulatory pathway involving circ_0002331, CCND2, and ELAVL1 in endothelial cells.
- To assess the therapeutic potential of circ_0002331 for AS.
Main Methods:
- Established an in vitro AS model using ox-LDL treated HUVECs.
- Quantified circ_0002331, CCND2, and ELAVL1 expression via qRT-PCR.
- Assessed cell function (proliferation, apoptosis, migration, invasion, angiogenesis) using various assays.
- Analyzed protein levels, RNA-protein interactions (RIP, RNA pull-down), and cellular localization (FISH).
Main Results:
- circ_0002331 expression was significantly downregulated in AS patients and ox-LDL treated HUVECs.
- Overexpressing circ_0002331 reversed ox-LDL induced HUVEC dysfunction, promoting beneficial functions and inhibiting detrimental ones.
- circ_0002331 positively regulated CCND2 and enhanced CCND2 mRNA stability by interacting with ELAVL1.
- CCND2's role was confirmed, as its overexpression mimicked protective effects, and knockdown reversed circ_0002331's benefits.
Conclusions:
- circ_0002331 acts as a protective factor against AS.
- The mechanism involves circ_0002331 binding ELAVL1 to stabilize CCND2 mRNA, thereby ameliorating endothelial cell dysfunction.
- circ_0002331 represents a promising therapeutic target for AS treatment.
Abstract:
Circular RNAs (circRNAs) have been discovered to serve as vital regulators in atherosclerosis (AS). However, the role and mechanism of circ_0002331 in AS process are still unclear. Human umbilical vein endothelial cells (HUVECs) were treated with ox-LDL to establish an in vitro model for AS. The expression levels of circ_0002331, Cyclin D2 (CCND2) and ELAVL1 were analyzed by quantitative real-time PCR. Cell proliferation, apoptosis, migration, invasion and angiogenesis were assessed by EdU assay, flow cytometry, transwell assay and tube formation assay. The protein levels of CCND2, ELAVL1, and autophagy-related markers were detected using western blot analysis. IL-8 level was analyzed by ELISA. The relationship between ELAVL1 and circ_0002331 or CCND2 was analyzed by RIP assay and RNA pull-down assay. Moreover, FISH assay was used to analyze the co-localization of ELAVL1 and CCND2 in HUVECs. Our data showed that circ_0002331 was obviously downregulated in AS patients and ox-LDL-induced HUVECs. Overexpression of circ_0002331 could promote proliferation, migration, invasion and angiogenesis, while inhibit apoptosis, autophagy and inflammation in ox-LDL-induced HUVECs. Furthermore, CCND2 was positively regulated by circ_0002331, and circ_0002331 could bind with ELAVL1 to promote CCND2 mRNA stability. Besides, CCND2 overexpression suppressed ox-LDL-induced HUVECs dysfunction, and its knockdown also reversed the regulation of circ_0002331 on ox-LDL-induced HUVECs dysfunction. In conclusion, circ_0002331 might be a potential target for AS treatment, which could improve ox-LDL-induced dysfunction of HUVECs via regulating CCND2 by binding with ELAVL1.
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