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A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis

Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence....

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Autores principales: Min, Xue, Cai, Meng‐yun, Shao, Tong, Xu, Zi‐yang, Liao, Zhaofu, Liu, Dong‐liang, Zhou, Meng‐yuan, Wu, Wei‐peng, Zhou, Yu‐lan, Mo, Miao‐hua, Xu, Shun, Liu, Xinguang, Xiong, Xing‐dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761008/
https://www.ncbi.nlm.nih.gov/pubmed/34902213
http://dx.doi.org/10.1111/acel.13529
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author Min, Xue
Cai, Meng‐yun
Shao, Tong
Xu, Zi‐yang
Liao, Zhaofu
Liu, Dong‐liang
Zhou, Meng‐yuan
Wu, Wei‐peng
Zhou, Yu‐lan
Mo, Miao‐hua
Xu, Shun
Liu, Xinguang
Xiong, Xing‐dong
author_facet Min, Xue
Cai, Meng‐yun
Shao, Tong
Xu, Zi‐yang
Liao, Zhaofu
Liu, Dong‐liang
Zhou, Meng‐yuan
Wu, Wei‐peng
Zhou, Yu‐lan
Mo, Miao‐hua
Xu, Shun
Liu, Xinguang
Xiong, Xing‐dong
author_sort Min, Xue
collection PubMed
description Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence. We observed significant downregulation of ciPVT1 in senescent endothelial cells. In proliferating endothelial cells, ciPVT1 knockdown induced a premature senescence‐like phenotype, inhibited proliferation, and led to an impairment in angiogenesis. An in vivo angiogenic plug assay revealed that ciPVT1 silencing significantly inhibited endothelial tube formation and decreased hemoglobin content. Conversely, overexpression of ciPVT1 in old endothelial cells delayed senescence, promoted proliferation, and increased angiogenic activity. Mechanistic studies revealed that ciPVT1 can sponge miR‐24‐3p to upregulate the expression of CDK4, resulting in enhanced Rb phosphorylation. Moreover, enforced expression of ciPVT1 reversed the senescence induction effect of miR‐24‐3p in endothelial cells. In summary, the present study reveals a pivotal role for ciPVT1 in regulating endothelial cell senescence and may have important implications in the search of strategies to counteract the development of age‐associated vascular pathologies.
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spelling pubmed-87610082022-01-20 A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis Min, Xue Cai, Meng‐yun Shao, Tong Xu, Zi‐yang Liao, Zhaofu Liu, Dong‐liang Zhou, Meng‐yuan Wu, Wei‐peng Zhou, Yu‐lan Mo, Miao‐hua Xu, Shun Liu, Xinguang Xiong, Xing‐dong Aging Cell Original Papers Circular RNAs (circRNAs) have been established to be involved in numerous processes in the human genome, but their function in vascular aging remains largely unknown. In this study, we aimed to characterize and analyze the function of a circular intronic RNA, ciPVT1, in endothelial cell senescence. We observed significant downregulation of ciPVT1 in senescent endothelial cells. In proliferating endothelial cells, ciPVT1 knockdown induced a premature senescence‐like phenotype, inhibited proliferation, and led to an impairment in angiogenesis. An in vivo angiogenic plug assay revealed that ciPVT1 silencing significantly inhibited endothelial tube formation and decreased hemoglobin content. Conversely, overexpression of ciPVT1 in old endothelial cells delayed senescence, promoted proliferation, and increased angiogenic activity. Mechanistic studies revealed that ciPVT1 can sponge miR‐24‐3p to upregulate the expression of CDK4, resulting in enhanced Rb phosphorylation. Moreover, enforced expression of ciPVT1 reversed the senescence induction effect of miR‐24‐3p in endothelial cells. In summary, the present study reveals a pivotal role for ciPVT1 in regulating endothelial cell senescence and may have important implications in the search of strategies to counteract the development of age‐associated vascular pathologies. John Wiley and Sons Inc. 2021-12-13 2022-01 /pmc/articles/PMC8761008/ /pubmed/34902213 http://dx.doi.org/10.1111/acel.13529 Text en © 2021 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Papers
Min, Xue
Cai, Meng‐yun
Shao, Tong
Xu, Zi‐yang
Liao, Zhaofu
Liu, Dong‐liang
Zhou, Meng‐yuan
Wu, Wei‐peng
Zhou, Yu‐lan
Mo, Miao‐hua
Xu, Shun
Liu, Xinguang
Xiong, Xing‐dong
A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis
title A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis
title_full A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis
title_fullStr A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis
title_full_unstemmed A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis
title_short A circular intronic RNA ciPVT1 delays endothelial cell senescence by regulating the miR‐24‐3p/CDK4/pRb axis
title_sort circular intronic rna cipvt1 delays endothelial cell senescence by regulating the mir‐24‐3p/cdk4/prb axis
topic Original Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8761008/
https://www.ncbi.nlm.nih.gov/pubmed/34902213
http://dx.doi.org/10.1111/acel.13529
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