circGNAQ, a circular RNA enriched in vascular endothelium, inhibits endothelial cell senescence and atherosclerosis progression
| Autor: | Xin Liang, Shun Xu, Dong-liang Liu, Xing-dong Xiong, Meng-yuan Zhou, Miaohua Mo, Xia Jing, Tong Shao, Wei-peng Wu, Zi-yang Xu, Xue Min, Meng-yun Cai, Xinguang Liu |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Senescence
Endothelium Cell growth Angiogenesis circGNAQ Endogeny circular RNA RM1-950 Biology Cell biology Endothelial stem cell medicine.anatomical_structure Circular RNA Drug Discovery medicine Molecular Medicine Gene silencing Original Article Therapeutics. Pharmacology atherosclerosis vascular endothelium endothelial cell senescence |
| Zdroj: | Molecular Therapy: Nucleic Acids, Vol 26, Iss, Pp 374-387 (2021) Molecular Therapy. Nucleic Acids |
| ISSN: | 2162-2531 |
| Popis: | 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. Graphical abstract Endothelial cell senescence is one of the most important causes of vascular dysfunction and atherosclerosis. We found that circGNAQ, a circular RNA enriched in vascular endothelium, inhibited endothelial cell senescence and atherosclerosis progression, implying that circGNAQ-based gene therapy could serve as a novel therapeutic strategy to protect against atherosclerosis development. |
| Databáze: | OpenAIRE |
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