circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression
Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. Circular RNAs (circRNAs) are endogenous RNA molecules with covalently closed-loop structures, which have been reported to be abnormally expressed in many human diseases. However, the potentia...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121001888 |
| _version_ | 1819202892021628928 |
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| author | Wei-peng Wu Meng-yuan Zhou Dong-liang Liu Xue Min Tong Shao Zi-yang Xu Xia Jing Meng-yun Cai Shun Xu Xin Liang Miaohua Mo Xinguang Liu Xing-dong Xiong |
| author_facet | Wei-peng Wu Meng-yuan Zhou Dong-liang Liu Xue Min Tong Shao Zi-yang Xu Xia Jing Meng-yun Cai Shun Xu Xin Liang Miaohua Mo Xinguang Liu Xing-dong Xiong |
| author_sort | Wei-peng Wu |
| collection | DOAJ |
| description | Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. Circular RNAs (circRNAs) are endogenous RNA molecules with covalently closed-loop structures, which have been reported to be abnormally expressed in many human diseases. However, the potential role of circRNAs in endothelial cell senescence and atherosclerosis remains largely unknown. Here, we compared the expression patterns of circRNAs in young and senescent human endothelial cells with RNA sequencing. Among the differentially expressed circRNAs, circGNAQ, a circRNA enriched in vascular endothelium, was significantly downregulated in senescent endothelial cells. circGNAQ silencing triggered endothelial cell senescence, as determined by a rise in senescence-associated β-galactosidase activity, reduced cell proliferation, and suppressed angiogenesis; circGNAQ overexpression showed the opposite effects. Mechanistic studies revealed that circGNAQ acted as an endogenous miR-146a-5p sponge to increase the expression of its target gene PLK2 by decoying the miR-146a-5p, thereby delaying endothelial cell senescence. In vivo studies showed that circGNAQ overexpression in the endothelium inhibited endothelial cell senescence and atherosclerosis progression. These results suggest that circGNAQ plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that the management of circGNAQ provides a potential therapeutic approach for limiting the progression of atherosclerosis. |
| first_indexed | 2024-12-23T04:11:14Z |
| format | Article |
| id | doaj.art-468ed261371b461f8503b9f60ed1302f |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-23T04:11:14Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-468ed261371b461f8503b9f60ed1302f2022-12-21T18:00:30ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-12-0126374387circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progressionWei-peng Wu0Meng-yuan Zhou1Dong-liang Liu2Xue Min3Tong Shao4Zi-yang Xu5Xia Jing6Meng-yun Cai7Shun Xu8Xin Liang9Miaohua Mo10Xinguang Liu11Xing-dong Xiong12Institute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. China; Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang 524023, P.R. ChinaInstitute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. China; Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang 524023, P.R. China; Corresponding author: Prof. Xing-dong Xiong, Institute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical University, Dongguan 523808, P.R. China.Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. Circular RNAs (circRNAs) are endogenous RNA molecules with covalently closed-loop structures, which have been reported to be abnormally expressed in many human diseases. However, the potential role of circRNAs in endothelial cell senescence and atherosclerosis remains largely unknown. Here, we compared the expression patterns of circRNAs in young and senescent human endothelial cells with RNA sequencing. Among the differentially expressed circRNAs, circGNAQ, a circRNA enriched in vascular endothelium, was significantly downregulated in senescent endothelial cells. circGNAQ silencing triggered endothelial cell senescence, as determined by a rise in senescence-associated β-galactosidase activity, reduced cell proliferation, and suppressed angiogenesis; circGNAQ overexpression showed the opposite effects. Mechanistic studies revealed that circGNAQ acted as an endogenous miR-146a-5p sponge to increase the expression of its target gene PLK2 by decoying the miR-146a-5p, thereby delaying endothelial cell senescence. In vivo studies showed that circGNAQ overexpression in the endothelium inhibited endothelial cell senescence and atherosclerosis progression. These results suggest that circGNAQ plays critical roles in endothelial cell senescence and consequently the pathogenesis of atherosclerosis, implying that the management of circGNAQ provides a potential therapeutic approach for limiting the progression of atherosclerosis.http://www.sciencedirect.com/science/article/pii/S2162253121001888circGNAQcircular RNAvascular endotheliumendothelial cell senescenceatherosclerosis |
| spellingShingle | Wei-peng Wu Meng-yuan Zhou Dong-liang Liu Xue Min Tong Shao Zi-yang Xu Xia Jing Meng-yun Cai Shun Xu Xin Liang Miaohua Mo Xinguang Liu Xing-dong Xiong circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression Molecular Therapy: Nucleic Acids circGNAQ circular RNA vascular endothelium endothelial cell senescence atherosclerosis |
| title | circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression |
| title_full | circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression |
| title_fullStr | circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression |
| title_full_unstemmed | circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression |
| title_short | circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression |
| title_sort | circgnaq a circular rna enriched in vascular endothelium inhibits endothelial cell senescence and atherosclerosis progression |
| topic | circGNAQ circular RNA vascular endothelium endothelial cell senescence atherosclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121001888 |
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