ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17
Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we inv...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Acta Pharmaceutica Sinica B |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383523002563 |
| _version_ | 1797454634583851008 |
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| author | Junting Zhang Yiying Li Jianchao Zhang Lu Liu Yuan Chen Xusheng Yang Xueyi Liao Muhua He Zihui Jia Jun Fan Jin-Song Bian Xiaowei Nie |
| author_facet | Junting Zhang Yiying Li Jianchao Zhang Lu Liu Yuan Chen Xusheng Yang Xueyi Liao Muhua He Zihui Jia Jun Fan Jin-Song Bian Xiaowei Nie |
| author_sort | Junting Zhang |
| collection | DOAJ |
| description | Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease. |
| first_indexed | 2024-03-09T15:40:59Z |
| format | Article |
| id | doaj.art-88862a56dcc14a8b816835401b0fd19f |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-03-09T15:40:59Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-88862a56dcc14a8b816835401b0fd19f2023-11-25T04:47:42ZengElsevierActa Pharmaceutica Sinica B2211-38352023-12-01131248404855ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17Junting Zhang0Yiying Li1Jianchao Zhang2Lu Liu3Yuan Chen4Xusheng Yang5Xueyi Liao6Muhua He7Zihui Jia8Jun Fan9Jin-Song Bian10Xiaowei Nie11Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China; Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou 510632, ChinaShenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China; Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou 510632, ChinaShenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China; Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaLung Transplant Group, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 211103, ChinaLung Transplant Group, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 211103, ChinaShenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China; Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, ChinaLung Transplant Group, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi 211103, ChinaDepartment of Medical Biochemistry and Molecular Biology, School of Medicine, Jinan University, Guangzhou 510632, ChinaDepartment of Pharmacology, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, China; Corresponding authors.Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People's Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen 518020, China; Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou 510632, China; Corresponding authors.Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.http://www.sciencedirect.com/science/article/pii/S2211383523002563Pulmonary hypertensionADAR1Circular RNAVascular remodelingCell proliferation |
| spellingShingle | Junting Zhang Yiying Li Jianchao Zhang Lu Liu Yuan Chen Xusheng Yang Xueyi Liao Muhua He Zihui Jia Jun Fan Jin-Song Bian Xiaowei Nie ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17 Acta Pharmaceutica Sinica B Pulmonary hypertension ADAR1 Circular RNA Vascular remodeling Cell proliferation |
| title | ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17 |
| title_full | ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17 |
| title_fullStr | ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17 |
| title_full_unstemmed | ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17 |
| title_short | ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17 |
| title_sort | adar1 regulates vascular remodeling in hypoxic pulmonary hypertension through n1 methyladenosine modification of circcdk17 |
| topic | Pulmonary hypertension ADAR1 Circular RNA Vascular remodeling Cell proliferation |
| url | http://www.sciencedirect.com/science/article/pii/S2211383523002563 |
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