JACC: Basic to Translational Science (Sep 2022)
A Novel LncRNA SNHG3 Promotes Osteoblast Differentiation Through BMP2 Upregulation in Aortic Valve Calcification
- Long Chen, MD,
- Hanning Liu, MD, PhD,
- Cheng Sun, MD, PhD,
- Jianqiu Pei, PhD,
- Jun Li, MD,
- Yue Li, PhD,
- Ke Wei, MD, PhD,
- Xiaoyi Wang, MD,
- Peng Wang, MD,
- Fangzhou Li, MD,
- Shujie Gai, MD, PhD,
- Yan Zhao, MD,
- Zhe Zheng, MD, PhD
Affiliations
- Long Chen, MD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Hanning Liu, MD, PhD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Cheng Sun, MD, PhD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Jianqiu Pei, PhD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Jun Li, MD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Yue Li, PhD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Ke Wei, MD, PhD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Xiaoyi Wang, MD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Peng Wang, MD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Fangzhou Li, MD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Shujie Gai, MD, PhD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Yan Zhao, MD
- Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Zhe Zheng, MD, PhD
- Address for correspondence: Dr Zhe Zheng, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167 Beilishi Road, Xicheng District, Beijing, PR China.; Department of Cardiovascular Surgery, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Disease, China and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
- Journal volume & issue
-
Vol. 7,
no. 9
pp. 899 – 914
Abstract
Summary: Based on high-throughput transcriptomic sequencing, SNHG3 was among the most highly expressed long noncoding RNAs in calcific aortic valve disease. SNHG3 upregulation was verified in human and mouse calcified aortic valves. Moreover, in vivo and in vitro studies showed SNHG3 silencing markedly ameliorated aortic valve calcification. In-depth functional assays showed SNHG3 physically interacted with polycomb repressive complex 2 to suppress the H3K27 trimethylation BMP2 locus, which in turn activated BMP2 expression and signaling pathways. Taken together, SNHG3 promoted aortic valve calcification by upregulating BMP2, which might be a novel therapeutic target in human calcific aortic valve disease.