Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells

Atherosclerosis (AS) is an inflammatory disease caused by multiple factors. Multiple circRNAs are involved in the development of AS. The present study focusses on delineating the role of circ_0090231 in AS. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox...

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Autores principales:	Yishan Ge, Wenwu Liu, Wei Yin, Xuebin Wang, Jie Wang, Xiaoqing Zhu, Shengkai Xu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	atherosclerosis circ_0090231 pyroptosis nlrp3 mir-635 Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/064649d0b85a4423a2c58d60b4f8dbbe
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spelling	oai:doaj.org-article:064649d0b85a4423a2c58d60b4f8dbbe2021-12-01T14:41:00ZCircular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells2165-59792165-598710.1080/21655979.2021.1989260https://doaj.org/article/064649d0b85a4423a2c58d60b4f8dbbe2021-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21655979.2021.1989260https://doaj.org/toc/2165-5979https://doaj.org/toc/2165-5987Atherosclerosis (AS) is an inflammatory disease caused by multiple factors. Multiple circRNAs are involved in the development of AS. The present study focusses on delineating the role of circ_0090231 in AS. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL) to construct an in vitro AS model. Real-time quantitative polymerase-chain reaction (RT-qPCR) was used to detect the levels of circ_0090231, IL-1β, and IL-18 transcripts. CircRNA/target gene interactions were predicted using StarBase and TargetScan and confirmed using an RNA pull-down assay and dual-luciferase reporter assay. Further, 3-(4,5)-dimethylthiahiazo(−2)-3,5-diphenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH) release assays were performed to evaluate cell viability and damage in the AS model, respectively. Cell pyroptosis and protein expression were determined using flow cytometry and western blotting respectively. The treatment of HAECs with ox-LDL not only led to significant increase in the levels of circ_0090231 but also resulted in improved cell viability as well as reduced cell injury and pyroptosis as compared to that in non-treated cells. The circ_0090231 was also identified to function as a sponge for miR-635, knockdown of which reverses the effects of circ_0090231 inhibition. Furthermore, our results revealed that levels of NLRP3, a miR-635 target, are not only augmented in the AS model but its overexpression also weakens the miR-635 regulatory effects in the AS development. Taken together, the circ_0090231/miR-635/NLRP3 axis affects the development of AS by regulating cell pyroptosis, thus providing new insights into the mechanism of AS development.Yishan GeWenwu LiuWei YinXuebin WangJie WangXiaoqing ZhuShengkai XuTaylor & Francis Grouparticleatherosclerosiscirc_0090231pyroptosisnlrp3mir-635BiotechnologyTP248.13-248.65ENBioengineered, Vol 12, Iss 2, Pp 10837-10848 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atherosclerosis circ_0090231 pyroptosis nlrp3 mir-635 Biotechnology TP248.13-248.65
spellingShingle	atherosclerosis circ_0090231 pyroptosis nlrp3 mir-635 Biotechnology TP248.13-248.65 Yishan Ge Wenwu Liu Wei Yin Xuebin Wang Jie Wang Xiaoqing Zhu Shengkai Xu Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells
description	Atherosclerosis (AS) is an inflammatory disease caused by multiple factors. Multiple circRNAs are involved in the development of AS. The present study focusses on delineating the role of circ_0090231 in AS. Human aortic endothelial cells (HAECs) were treated with oxidized low-density lipoprotein (ox-LDL) to construct an in vitro AS model. Real-time quantitative polymerase-chain reaction (RT-qPCR) was used to detect the levels of circ_0090231, IL-1β, and IL-18 transcripts. CircRNA/target gene interactions were predicted using StarBase and TargetScan and confirmed using an RNA pull-down assay and dual-luciferase reporter assay. Further, 3-(4,5)-dimethylthiahiazo(−2)-3,5-diphenytetrazoliumromide (MTT) and lactate dehydrogenase (LDH) release assays were performed to evaluate cell viability and damage in the AS model, respectively. Cell pyroptosis and protein expression were determined using flow cytometry and western blotting respectively. The treatment of HAECs with ox-LDL not only led to significant increase in the levels of circ_0090231 but also resulted in improved cell viability as well as reduced cell injury and pyroptosis as compared to that in non-treated cells. The circ_0090231 was also identified to function as a sponge for miR-635, knockdown of which reverses the effects of circ_0090231 inhibition. Furthermore, our results revealed that levels of NLRP3, a miR-635 target, are not only augmented in the AS model but its overexpression also weakens the miR-635 regulatory effects in the AS development. Taken together, the circ_0090231/miR-635/NLRP3 axis affects the development of AS by regulating cell pyroptosis, thus providing new insights into the mechanism of AS development.
format	article
author	Yishan Ge Wenwu Liu Wei Yin Xuebin Wang Jie Wang Xiaoqing Zhu Shengkai Xu
author_facet	Yishan Ge Wenwu Liu Wei Yin Xuebin Wang Jie Wang Xiaoqing Zhu Shengkai Xu
author_sort	Yishan Ge
title	Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells
title_short	Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells
title_full	Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells
title_fullStr	Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells
title_full_unstemmed	Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells
title_sort	circular rna circ_0090231 promotes atherosclerosis in vitro by enhancing nlr family pyrin domain containing 3-mediated pyroptosis of endothelial cells
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/064649d0b85a4423a2c58d60b4f8dbbe
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_version_	1718404976075603968

Circular RNA circ_0090231 promotes atherosclerosis in vitro by enhancing NLR family pyrin domain containing 3-mediated pyroptosis of endothelial cells

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