Silencing hsa_Circ_0007478 Regulates EFNA3 Expression to Alleviate the ox-LDL-Induced Inflammatory Response by Sponging miR-765 in Macrophages

Background: Circular RNAs (circRNA), a novel class of RNAs, are a group of nonprotein-encoding RNA molecules capable of regulating mRNA expression at the posttranscriptional level. Rapidly growing evidence presented that some circRNAs are responsible for cardiovascular disease by playing a role as ceRNAs. However, little is known about circRNA the function of circRNAs in atherosclerosis(AS). Methods: Gene Expression Omnibus (GEO) database was applied to screen differentially expressed circRNAs of the normal macrophage group and the ox-LDL-stimulated group. CircInteractome, TargetScan and miRecords websites were used to predict target relationships. Findings: We found that hsa_circ_0007478 was upregulated in ox-LDL-stimulated macrophages, and compared with the ox-LDL-stimulated macrophage group, the protein level of NLRP3 and IL-1I² in macrophages was decreased and the activation of NF-IoB was inhibited in si-hsa_circ_0007478 group. Hsa_circ_0007478 has a base-pairing relationship with miR-765 through bioinformatics analysis. Furthermore, by modulating the hsa_circ_0007478 and the miR-765 level, it was indicated that hsa_circ_0007478 regulate EFNA3 expression to alleviate ox-LDL Induced inflammatory response by sponging miR765 in macrophages. Interpretation: This result indicates that the suppression of the hsa_circ_0007478/miR-765/EFNA3 axis alleviates inflammatory responses in ox-LDL-stimulated macrophages. Considering that hsa_circ_0007478 has a stable and conservative structure, our results provide a molecular basis and potential therapeutic target for relieving atherosclerotic progression. Funding: This study was supported by the National Natural Science Foundation of China (Grant No. 81670227 and 81600341) and the Wenzhou Science and Technology Bureau (Grant No. Y20170045 and Y20180099). Declaration of Interest: There is none of any conflict of interest, financial or otherwise, related to the submitted work. Ethical Approval: Not required.