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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals
2021
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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. |
format | Online Article Text |
id | pubmed-7950295 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Impact Journals |
record_format | MEDLINE/PubMed |
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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