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CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract

Ultraviolet B (UVB) irradiation could trigger DNA double-strand breaks (DDSBs) and senescence in lens epithelial cells (LECs), thus inducing age-related cortical cataract (ARCC) formation. Cell-cycle irreversible arrest induced by DDSBs depended on excessive activation of ataxia-telangiectasia mutat...

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Autores principales: Liu, Junliang, Zhang, Jinling, Zhang, Guowei, Zhou, Tianqiu, Zou, Xi, Guan, Huaijin, Wang, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950295/
https://www.ncbi.nlm.nih.gov/pubmed/33508783
http://dx.doi.org/10.18632/aging.202470
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author Liu, Junliang
Zhang, Jinling
Zhang, Guowei
Zhou, Tianqiu
Zou, Xi
Guan, Huaijin
Wang, Yong
author_facet Liu, Junliang
Zhang, Jinling
Zhang, Guowei
Zhou, Tianqiu
Zou, Xi
Guan, Huaijin
Wang, Yong
author_sort Liu, Junliang
collection PubMed
description Ultraviolet B (UVB) irradiation could trigger DNA double-strand breaks (DDSBs) and senescence in lens epithelial cells (LECs), thus inducing age-related cortical cataract (ARCC) formation. Cell-cycle irreversible arrest induced by DDSBs depended on excessive activation of ataxia-telangiectasia mutated kinase (ATM). We studied the up-regulated circular RNA circMRE11A_013 (circMRE11A) in LECs of ARCC and SRA01/04 cell lines under UVB exposure. In vitro, knockdown of circMRE11A in SRA01/04 cell lines enhanced cell viability and cell cycle, while over-expression of circMRE11A exhibited an opposite trend. Additionally, circMRE11A could bind to UBX domain-containing protein 1 (UBXN1), which might enhance excessive activation of ATM and initiate ATM/p53/p21 signaling pathway causing LECs cell-cycle arrest and senescence. In vivo, recombinant adeno-associated virus vectors (rAAV-2) virions of circMRE11A (circMRE11A-AAV2) was injected to Institute of Cancer Research mouse vitreous cavity. The circMRE11A-AAV2 could express in mouse lens at 4 weeks. The LECs aging and opacity lens were observed at 8 weeks after the injection. Together, our findings reveal a previously unidentified role of circMRE11A interacting with UBXN1 in enhancing ATM activity and inhibiting LECs cell-cycle in ARCC formation. The findings might give us a better understanding of ARC pathology and provide a novel and more effective therapeutic approaches for ARC treatment.
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spelling pubmed-79502952021-03-23 CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract Liu, Junliang Zhang, Jinling Zhang, Guowei Zhou, Tianqiu Zou, Xi Guan, Huaijin Wang, Yong Aging (Albany NY) Research Paper Ultraviolet B (UVB) irradiation could trigger DNA double-strand breaks (DDSBs) and senescence in lens epithelial cells (LECs), thus inducing age-related cortical cataract (ARCC) formation. Cell-cycle irreversible arrest induced by DDSBs depended on excessive activation of ataxia-telangiectasia mutated kinase (ATM). We studied the up-regulated circular RNA circMRE11A_013 (circMRE11A) in LECs of ARCC and SRA01/04 cell lines under UVB exposure. In vitro, knockdown of circMRE11A in SRA01/04 cell lines enhanced cell viability and cell cycle, while over-expression of circMRE11A exhibited an opposite trend. Additionally, circMRE11A could bind to UBX domain-containing protein 1 (UBXN1), which might enhance excessive activation of ATM and initiate ATM/p53/p21 signaling pathway causing LECs cell-cycle arrest and senescence. In vivo, recombinant adeno-associated virus vectors (rAAV-2) virions of circMRE11A (circMRE11A-AAV2) was injected to Institute of Cancer Research mouse vitreous cavity. The circMRE11A-AAV2 could express in mouse lens at 4 weeks. The LECs aging and opacity lens were observed at 8 weeks after the injection. Together, our findings reveal a previously unidentified role of circMRE11A interacting with UBXN1 in enhancing ATM activity and inhibiting LECs cell-cycle in ARCC formation. The findings might give us a better understanding of ARC pathology and provide a novel and more effective therapeutic approaches for ARC treatment. Impact Journals 2021-01-28 /pmc/articles/PMC7950295/ /pubmed/33508783 http://dx.doi.org/10.18632/aging.202470 Text en Copyright: © 2021 Liu et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Liu, Junliang
Zhang, Jinling
Zhang, Guowei
Zhou, Tianqiu
Zou, Xi
Guan, Huaijin
Wang, Yong
CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract
title CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract
title_full CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract
title_fullStr CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract
title_full_unstemmed CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract
title_short CircMRE11A_013 binds to UBXN1 and integrates ATM activation enhancing lens epithelial cells senescence in age-related cataract
title_sort circmre11a_013 binds to ubxn1 and integrates atm activation enhancing lens epithelial cells senescence in age-related cataract
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7950295/
https://www.ncbi.nlm.nih.gov/pubmed/33508783
http://dx.doi.org/10.18632/aging.202470
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