A Novel LncRNA SNHG3 Promotes Osteoblast Differentiation Through BMP2 Upregulation in Aortic Valve Calcification

Long Chen; Hanning Liu; Cheng Sun; Jianqiu Pei; Jun Li; Yue Li; Ke Wei; Xiaoyi Wang; Peng Wang; Fangzhou Li; Shujie Gai; Yan Zhao; Zhe Zheng

doi:10.1016/j.jacbts.2022.06.009

A Novel LncRNA SNHG3 Promotes Osteoblast Differentiation Through BMP2 Upregulation in Aortic Valve Calcification

JACC Basic Transl Sci. 2022 Sep 26;7(9):899-914. doi: 10.1016/j.jacbts.2022.06.009. eCollection 2022 Sep.

Authors

Long Chen¹, Hanning Liu¹, Cheng Sun¹, Jianqiu Pei¹, Jun Li¹, Yue Li¹, Ke Wei¹, Xiaoyi Wang¹, Peng Wang¹, Fangzhou Li¹, Shujie Gai¹, Yan Zhao¹, Zhe Zheng¹

Affiliation

¹ 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.

Abstract

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.

Keywords: ADV, adenovirus; ALP, alkaline phosphatase; ASO, antisense oligonucleotide; ApoE−/−, apolipoprotein E-deficient; BMP, bone morphogenic proteins; BMP2 pathway; CAVD, calcific aortic valve disease; EZH2, enhancer of zeste 2; FISH, fluorescence in situ hybridization; HCD, high-cholesterol diet; ND, normal diet; PRC2, polycomb repressive complex 2; RT-qPCR, reverse-transcriptase-quantitative polymerase chain reaction; RUNX2, Runt-related transcription factor 2; SNHG3, small nucleolar RNA host gene 3; TGF, transforming growth factor; calcific aortic valve disease; hVICs, human aortic valve interstitial cells; lncRNA, long noncoding RNA; long noncoding RNA; osteoblast differentiation; therapeutic target.