circ_0086296 induced atherosclerotic lesions via the IFIT1/STAT1 feedback loop by sponging miR-576-3p

Autor: Min Zhang, Yiqian Zhu, Jie Zhu, Yi Xie, Ruihao Wu, JiaYin Zhong, Zhaohui Qiu, Li Jiang
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cellular & Molecular Biology Letters, Vol 27, Iss 1, Pp 1-26 (2022)
Druh dokumentu: article
ISSN: 1425-8153
1689-1392
DOI: 10.1186/s11658-022-00372-2
Popis: Abstract Extensive inflammation of endothelial cells (ECs) facilitates atherosclerotic lesion formation. Circular RNA (circRNA) participates in atherosclerosis (AS)-related inflammation responses; however, whether and how circ_0086296 regulates atherosclerotic inflammation and lesions have not been investigated. Microarray analysis, quantitative real-time polymerase chain reaction, and fluorescence in situ hybridization assay were performed to detect the expression and location of hsa_circ_0086296 in human carotid artery plaques, aorta of atherosclerotic mice, and human umbilical vein endothelial cells (HUVECs). Sanger sequencing was used to verify the loop structure of circ_0086296. The relationship among circ_0086296, miR-576-3p, IFIT1, STAT1, and EIF4A3 was validated using bioinformatics, luciferase assay, RNA pull-down assay, and RNA immunoprecipitation. The atherosclerosis mouse model was used to evaluate the function of circ_0086296 in vivo. circ_0086296 expression was significantly upregulated in human carotid artery plaques, oxidized low-density lipoprotein (ox-LDL)-treated HUVECs, and the aorta of atherosclerotic mice. Functional analysis indicated that circ_0086296 promotes ECs injury in vitro and atherosclerosis progression in vivo. The mechanism analysis indicated that circ_0086296 sponged miR-576-3p to promote IFIT1–STAT1 expression. Moreover, STAT1 upregulated circ_0086296 expression, forming the circ_0086296/miR-576-3p/IFIT1/STAT1 feedback loop. Notably, inhibition of the circ_0086296/miR-576-3p/IFIT1 axis could block atherosclerotic lesion formation both in vivo and in vitro. Finally, circ_0086296 was overexpressed in exosomes of patients with atherosclerosis and exosomes of ox-LDL-treated ECs. Therefore, the circ_0086296/miR-576-3p/IFIT1/STAT1 feedback loop participates in atherosclerosis progression and contributes to the high circ_0086296 expression observed in the exosomes of serum of patients with atherosclerosis. This study sought to provide a deep understanding of the mechanisms underlying the aberrant EC phenotype in AS.
Databáze: Directory of Open Access Journals
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