lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis

Introduction In this study, we investigated the role of the long non-coding RNA GAPLINC in atherosclerosis under oxidized low-density lipoprotein (ox-LDL) treatment. Material and methods We utilized ox-LDL exposed human aortic endothelial cells as an in-vitro model. The expression level of GAPLINC...

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Main Authors: Jun Pan, Bing Wang, Xibin Pu, Chenyang Qiu, Donglin Li, Ziheng Wu, Hongkun Zhang, Yangyan He
Format: Article
Language:English
Published: Termedia Publishing House 2023-07-01
Series:Archives of Medical Science
Subjects:
Online Access:https://www.archivesofmedicalscience.com/lncRNA-GAPLINC-regulates-vascular-endothelial-cell-apoptosis-in-atherosclerosis,169383,0,2.html
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author Jun Pan
Bing Wang
Xibin Pu
Chenyang Qiu
Donglin Li
Ziheng Wu
Hongkun Zhang
Yangyan He
author_facet Jun Pan
Bing Wang
Xibin Pu
Chenyang Qiu
Donglin Li
Ziheng Wu
Hongkun Zhang
Yangyan He
author_sort Jun Pan
collection DOAJ
description Introduction In this study, we investigated the role of the long non-coding RNA GAPLINC in atherosclerosis under oxidized low-density lipoprotein (ox-LDL) treatment. Material and methods We utilized ox-LDL exposed human aortic endothelial cells as an in-vitro model. The expression level of GAPLINC was quantified by qPCR in different times and concentrations of ox-LDL treatment conditions. Cell apoptosis rate and cell cycle profiles were assessed by flow cytometry and TUNEL assay. The target association was confirmed using a luciferase reporter assay and Western blot. Results We found that GAPLINC expression was induced by ox-LDL treatment, but cell proliferation ability was significantly inhibited. We further confirmed that overexpressing of lncRNA GAPLINC in ox-LDL-exposed HAECs decreased cell proliferation by increasing cell apoptosis and arresting cell cycle in G2/M and S phase. Importantly, the detailed mechanistic analysis elucidated that LncRNA GAPLINC acts as a decoy to sequester miR-183-5p to prevent it from binding to target PDCD4. MiR-183-5p targets GAPLINC, and PDCD4 is a downstream target of miR-183-5p, and the cellular effects of this direct interaction were confirmed by a rescue assay experiment. Conclusions The present study demonstrates that upregulation of lncRNA GAPLINC represses the binding of miR-183-5p to the PDCD4 promoter region and then promotes PDCD4 expression, thereby inducing cell apoptosis and suppressing endothelial cell proliferation.
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spelling doaj.art-976d89ada7ff4eb6b7101eaa77fc01d62024-04-11T08:11:16ZengTermedia Publishing HouseArchives of Medical Science1734-19221896-91512023-07-0120121623210.5114/aoms/169383169383lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosisJun Pan0Bing Wang1Xibin Pu2Chenyang Qiu3Donglin Li4Ziheng Wu5Hongkun Zhang6Yangyan He7Department of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaDepartment of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, ChinaIntroduction In this study, we investigated the role of the long non-coding RNA GAPLINC in atherosclerosis under oxidized low-density lipoprotein (ox-LDL) treatment. Material and methods We utilized ox-LDL exposed human aortic endothelial cells as an in-vitro model. The expression level of GAPLINC was quantified by qPCR in different times and concentrations of ox-LDL treatment conditions. Cell apoptosis rate and cell cycle profiles were assessed by flow cytometry and TUNEL assay. The target association was confirmed using a luciferase reporter assay and Western blot. Results We found that GAPLINC expression was induced by ox-LDL treatment, but cell proliferation ability was significantly inhibited. We further confirmed that overexpressing of lncRNA GAPLINC in ox-LDL-exposed HAECs decreased cell proliferation by increasing cell apoptosis and arresting cell cycle in G2/M and S phase. Importantly, the detailed mechanistic analysis elucidated that LncRNA GAPLINC acts as a decoy to sequester miR-183-5p to prevent it from binding to target PDCD4. MiR-183-5p targets GAPLINC, and PDCD4 is a downstream target of miR-183-5p, and the cellular effects of this direct interaction were confirmed by a rescue assay experiment. Conclusions The present study demonstrates that upregulation of lncRNA GAPLINC represses the binding of miR-183-5p to the PDCD4 promoter region and then promotes PDCD4 expression, thereby inducing cell apoptosis and suppressing endothelial cell proliferation.https://www.archivesofmedicalscience.com/lncRNA-GAPLINC-regulates-vascular-endothelial-cell-apoptosis-in-atherosclerosis,169383,0,2.htmllong non-coding rnagaplincox-ldlatherosclerosiscell apoptosis
spellingShingle Jun Pan
Bing Wang
Xibin Pu
Chenyang Qiu
Donglin Li
Ziheng Wu
Hongkun Zhang
Yangyan He
lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis
Archives of Medical Science
long non-coding rna
gaplinc
ox-ldl
atherosclerosis
cell apoptosis
title lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis
title_full lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis
title_fullStr lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis
title_full_unstemmed lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis
title_short lncRNA GAPLINC regulates vascular endothelial cell apoptosis in atherosclerosis
title_sort lncrna gaplinc regulates vascular endothelial cell apoptosis in atherosclerosis
topic long non-coding rna
gaplinc
ox-ldl
atherosclerosis
cell apoptosis
url https://www.archivesofmedicalscience.com/lncRNA-GAPLINC-regulates-vascular-endothelial-cell-apoptosis-in-atherosclerosis,169383,0,2.html
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