Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis
Endothelial pyroptosis is a pathological mechanism of atherosclerosis (AS). Circular RNAs (circRNAs) are vital in AS progression by regulating endothelial cell functions. The study aimed to explore whether circ-USP9× regulated pyroptosis of endothelial cell to involve in AS development and the molec...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Clinical and Experimental Hypertension |
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| Online Access: | http://dx.doi.org/10.1080/10641963.2023.2186319 |
| _version_ | 1797681057802223616 |
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| author | Shengkai Xu Yishan Ge Xuebin Wang Wei Yin Xiaoqing Zhu Jie Wang Shigang Qiao |
| author_facet | Shengkai Xu Yishan Ge Xuebin Wang Wei Yin Xiaoqing Zhu Jie Wang Shigang Qiao |
| author_sort | Shengkai Xu |
| collection | DOAJ |
| description | Endothelial pyroptosis is a pathological mechanism of atherosclerosis (AS). Circular RNAs (circRNAs) are vital in AS progression by regulating endothelial cell functions. The study aimed to explore whether circ-USP9× regulated pyroptosis of endothelial cell to involve in AS development and the molecular mechanism. Pyroptosis was determined using lactate dehydrogenase (LDH) assay, enzyme linked immunosorbent assay (ELISA), flow cytometry, propidium iodide (PI) staining assay, and western blot. The mechanism of circ-USP9× was determined using RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays. Results showed that circ-USP9× was upregulated in AS and oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of circ-USP9× suppressed ox-LDL induced pyroptosis of HUVECs. Mechanically, circ-USP9× could bind to EIF4A3 in the cytoplasm. Moreover, EIF4A3 was bound to GSDMD and further affects GSDMD stability. Overexpression of EIF4A3 rescued cell pyroptosis induced by circ-USP9× depletion. In short, circ-USP9× interacted with EIF4A3 to enhance GSDMD stability, thus further promoting ox-LDL-induced pyroptosis of HUVECs. These findings suggested that circ-USP9× participates in AS progression and may be a potential therapeutic target for AS. |
| first_indexed | 2024-03-11T23:39:22Z |
| format | Article |
| id | doaj.art-e203ea4338eb4f298a0b5d6e72d9c20d |
| institution | Directory Open Access Journal |
| issn | 1064-1963 1525-6006 |
| language | English |
| last_indexed | 2024-03-11T23:39:22Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Clinical and Experimental Hypertension |
| spelling | doaj.art-e203ea4338eb4f298a0b5d6e72d9c20d2023-09-19T16:04:08ZengTaylor & Francis GroupClinical and Experimental Hypertension1064-19631525-60062023-12-0145110.1080/10641963.2023.21863192186319Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosisShengkai Xu0Yishan Ge1Xuebin Wang2Wei Yin3Xiaoqing Zhu4Jie Wang5Shigang Qiao6Suzhou Science and Technology City HospitalSuzhou Science and Technology City HospitalSuzhou Science and Technology City HospitalSuzhou Science and Technology City HospitalSuzhou Science and Technology City HospitalSuzhou Science and Technology City HospitalSuzhou Science and Technology City HospitalEndothelial pyroptosis is a pathological mechanism of atherosclerosis (AS). Circular RNAs (circRNAs) are vital in AS progression by regulating endothelial cell functions. The study aimed to explore whether circ-USP9× regulated pyroptosis of endothelial cell to involve in AS development and the molecular mechanism. Pyroptosis was determined using lactate dehydrogenase (LDH) assay, enzyme linked immunosorbent assay (ELISA), flow cytometry, propidium iodide (PI) staining assay, and western blot. The mechanism of circ-USP9× was determined using RNA pull-down and RNA binding protein immunoprecipitation (RIP) assays. Results showed that circ-USP9× was upregulated in AS and oxidized low-density lipoprotein (ox-LDL)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of circ-USP9× suppressed ox-LDL induced pyroptosis of HUVECs. Mechanically, circ-USP9× could bind to EIF4A3 in the cytoplasm. Moreover, EIF4A3 was bound to GSDMD and further affects GSDMD stability. Overexpression of EIF4A3 rescued cell pyroptosis induced by circ-USP9× depletion. In short, circ-USP9× interacted with EIF4A3 to enhance GSDMD stability, thus further promoting ox-LDL-induced pyroptosis of HUVECs. These findings suggested that circ-USP9× participates in AS progression and may be a potential therapeutic target for AS.http://dx.doi.org/10.1080/10641963.2023.2186319atherosclerosispyroptosisendothelial cellscirc-usp9xgsdmd |
| spellingShingle | Shengkai Xu Yishan Ge Xuebin Wang Wei Yin Xiaoqing Zhu Jie Wang Shigang Qiao Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis Clinical and Experimental Hypertension atherosclerosis pyroptosis endothelial cells circ-usp9x gsdmd |
| title | Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis |
| title_full | Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis |
| title_fullStr | Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis |
| title_full_unstemmed | Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis |
| title_short | Circ-USP9X interacts with EIF4A3 to promote endothelial cell pyroptosis by regulating GSDMD stability in atherosclerosis |
| title_sort | circ usp9x interacts with eif4a3 to promote endothelial cell pyroptosis by regulating gsdmd stability in atherosclerosis |
| topic | atherosclerosis pyroptosis endothelial cells circ-usp9x gsdmd |
| url | http://dx.doi.org/10.1080/10641963.2023.2186319 |
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