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IUBMB Life ; 73(1): 177-187, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33249762

RESUMO

Circular RNAs (circRNAs) are a group of RNAs featured by a covalently closed continuous loop structure. This study aimed to uncover the function and mechanism of circ-ubiquitin specific peptidase 36 (USP36) in endothelial cells treated with oxidized low-density lipoprotein (ox-LDL). The levels of circ-USP36, microRNA-98-5p (miR-98-5p) and vascular cell adhesion molecule 1 (VCAM1) were examined by a quantitative real-time polymerase chain reaction (qRT-PCR). The viability, apoptosis and inflammation were detected by (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. Western blot assay was performed to detect the expression of apoptosis and proliferation-related markers and VCAM1 protein level. The targets of circ-USP36 and miR-98-5p were searched using starBase website, and dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to validate the above predictions. Ox-LDL exposure induced the upregulation of circ-USP36 in HUVEC cells. Circ-USP36 accelerated ox-LDL-induced apoptosis, inflammatory and viability inhibition of HUVEC cells. MiR-98-5p was a direct downstream gene of circ-USP36. Circ-USP36 promoted the injury of ox-LDL-induced HUVEC cells through targeting miR-98-5p. VCAM1 could bind to miR-98-5p, and the protective effects of miR-98-5p accumulation on ox-LDL-induced HUVEC cells were reversed by the transfection of VCAM1. VCAM1 was regulated by circ-USP36/miR-98-5p signaling in HUVEC cells. Ox-LDL promoted the apoptosis and inflammation but suppressed the viability of HUVEC cells through upregulating circ-USP36, thus elevating the expression of VCAM1 via miR-98-5p.


Assuntos
Endotélio Vascular/patologia , Inflamação/patologia , Lipoproteínas LDL/efeitos adversos , MicroRNAs/genética , RNA Circular/genética , Ubiquitina Tiolesterase/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Apoptose , Proliferação de Células , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/lesões , Endotélio Vascular/metabolismo , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Transdução de Sinais , Molécula 1 de Adesão de Célula Vascular/genética
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