In:
Journal of Cardiovascular Pharmacology, Ovid Technologies (Wolters Kluwer Health), Vol. 78, No. 5 ( 2021-11), p. e761-e772
Abstract:
Circular RNAs (circRNAs) are reported to play pivotal regulatory roles in atherosclerosis progression. In the present study, we explored the biological role of circRNA ubiquitin-specific peptidase 36 (circ_USP36; hsa_circ_0003204) in oxidized low-density lipoprotein (ox-LDL)-induced dysfunction of endothelial cells (ECs). RNA and protein levels were determined by reverse transcription-quantitative polymerase chain reaction and Western blot assay, respectively. Cell proliferation was analyzed by 5-ethynyl-2′-deoxyuridine assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was conducted to analyze cell cycle progression and cell apoptosis. The release of tumor necrosis factor α in the supernatant was measured by enzyme linked immunosorbent assay. Cell death was evaluated by lactate dehydrogenase assay. Intermolecular interaction was verified by dual-luciferase reporter assay. Circ_USP36 expression was significantly up-regulated in the serum of atherosclerosis patients and ox-LDL-stimulated HUVECs than that in their corresponding controls. ox-LDL exposure inhibited the proliferation ability and cell cycle progression and triggered the apoptosis and inflammation of HUVECs, and these effects were largely overturned by the knockdown of circ_USP36. microRNA-197-3p (miR-197-3p) was a target of circ_USP36, and circ_USP36 knockdown-mediated protective role in ox-LDL-induced HUVECs was largely counteracted by the silence of miR-197-3p. miR-197-3p interacted with the 3′ untranslated region of roundabout guidance receptor 1 (ROBO1). Circ_USP36 knockdown reduced ROBO1 expression partly by up-regulating miR-197-3p in HUVECs. ROBO1 overexpression reversed miR-197-3p accumulation-mediated effects in ox-LDL-induced HUVECs. In conclusion, circ_USP36 interference alleviated ox-LDL-induced dysfunction in HUVECs by targeting miR-197-3p/ROBO1 axis.
Type of Medium:
Online Resource
ISSN:
0160-2446
DOI:
10.1097/FJC.0000000000001124
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2021
detail.hit.zdb_id:
2049700-3
SSG:
15,3
