Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis

The circ_UBR4 (hsa_circ_0010283) is a novel abnormally overexpressed circRNA in oxidized low-density lipoprotein (ox-LDL)-induced model of atherosclerosis (AS) in human vascular smooth muscle cells (VSMCs). However, its role in the dysfunction of VSMCs remains to be further investigated. Here, we at...

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Autores principales: Zhang Ying, Zhang Cheng, Chen Zongwei, Wang Meilan
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Publicado: De Gruyter 2021
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spelling oai:doaj.org-article:8985149e3f8e432abf261b4f0acfe9c12021-12-05T14:10:41ZBlocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis2391-541210.1515/biol-2021-0044https://doaj.org/article/8985149e3f8e432abf261b4f0acfe9c12021-04-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0044https://doaj.org/toc/2391-5412The circ_UBR4 (hsa_circ_0010283) is a novel abnormally overexpressed circRNA in oxidized low-density lipoprotein (ox-LDL)-induced model of atherosclerosis (AS) in human vascular smooth muscle cells (VSMCs). However, its role in the dysfunction of VSMCs remains to be further investigated. Here, we attempted to explore its role in ox-LDL-induced excessive proliferation and migration in VSMCs by regulating Rho/Rho-associated coiled-coil containing kinase 1 (ROCK1), a therapeutic target of AS. Expression of circ_UBR4 and ROCK1 was upregulated, whereas miR-107 was downregulated in human AS serum and ox-LDL-induced VSMCs. Depletion of circ_UBR4 arrested cell cycle, suppressed cell viability, colony-forming ability, and migration ability, and depressed expression of proliferating cell nuclear antigen and matrix metalloproteinase 2 in VSMCs in spite of the opposite effects of ox-LDL. Notably, ROCK1 upregulation mediated by plasmid transfection or miR-107 deletion could counteract the suppressive role of circ_UBR4 knockdown in ox-LDL-induced VSMCs proliferation, migration, and cell cycle progression. In mechanism, miR-107 was identified as a target of circ_UBR4 to mediate the regulatory effect of circ_UBR4 on ROCK1. circ_UBR4 might be a contributor in human AS partially by regulating VSMCs’ cell proliferation, migration, and cell cycle progression via circ_UBR4/miR-107/ROCK1 pathway.Zhang YingZhang ChengChen ZongweiWang MeilanDe Gruyterarticlecirc_ubr4mir-107rock1atherosclerosisvsmcsBiology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 419-430 (2021)
institution DOAJ
collection DOAJ
language EN
topic circ_ubr4
mir-107
rock1
atherosclerosis
vsmcs
Biology (General)
QH301-705.5
spellingShingle circ_ubr4
mir-107
rock1
atherosclerosis
vsmcs
Biology (General)
QH301-705.5
Zhang Ying
Zhang Cheng
Chen Zongwei
Wang Meilan
Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
description The circ_UBR4 (hsa_circ_0010283) is a novel abnormally overexpressed circRNA in oxidized low-density lipoprotein (ox-LDL)-induced model of atherosclerosis (AS) in human vascular smooth muscle cells (VSMCs). However, its role in the dysfunction of VSMCs remains to be further investigated. Here, we attempted to explore its role in ox-LDL-induced excessive proliferation and migration in VSMCs by regulating Rho/Rho-associated coiled-coil containing kinase 1 (ROCK1), a therapeutic target of AS. Expression of circ_UBR4 and ROCK1 was upregulated, whereas miR-107 was downregulated in human AS serum and ox-LDL-induced VSMCs. Depletion of circ_UBR4 arrested cell cycle, suppressed cell viability, colony-forming ability, and migration ability, and depressed expression of proliferating cell nuclear antigen and matrix metalloproteinase 2 in VSMCs in spite of the opposite effects of ox-LDL. Notably, ROCK1 upregulation mediated by plasmid transfection or miR-107 deletion could counteract the suppressive role of circ_UBR4 knockdown in ox-LDL-induced VSMCs proliferation, migration, and cell cycle progression. In mechanism, miR-107 was identified as a target of circ_UBR4 to mediate the regulatory effect of circ_UBR4 on ROCK1. circ_UBR4 might be a contributor in human AS partially by regulating VSMCs’ cell proliferation, migration, and cell cycle progression via circ_UBR4/miR-107/ROCK1 pathway.
format article
author Zhang Ying
Zhang Cheng
Chen Zongwei
Wang Meilan
author_facet Zhang Ying
Zhang Cheng
Chen Zongwei
Wang Meilan
author_sort Zhang Ying
title Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
title_short Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
title_full Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
title_fullStr Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
title_full_unstemmed Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
title_sort blocking circ_ubr4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
publisher De Gruyter
publishDate 2021
url https://doaj.org/article/8985149e3f8e432abf261b4f0acfe9c1
work_keys_str_mv AT zhangying blockingcircubr4suppressedproliferationmigrationandcellcycleprogressionofhumanvascularsmoothmusclecellsinatherosclerosis
AT zhangcheng blockingcircubr4suppressedproliferationmigrationandcellcycleprogressionofhumanvascularsmoothmusclecellsinatherosclerosis
AT chenzongwei blockingcircubr4suppressedproliferationmigrationandcellcycleprogressionofhumanvascularsmoothmusclecellsinatherosclerosis
AT wangmeilan blockingcircubr4suppressedproliferationmigrationandcellcycleprogressionofhumanvascularsmoothmusclecellsinatherosclerosis
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