A Novel Hidden Protein p-414aa Encoded by <i>circSETD2(14,15</i> ) Inhibits Vascular Remodeling
Abstract
BACKGROUND: Phenotypic switching of vascular smooth muscle cells (VSMCs), leading to neointimal hyperplasia, is a fundamental cause of vascular remodeling diseases such as atherosclerosis and hypertension. Novel hidden proteins encoded by circular RNAs play crucial roles in disease progression, yet their involvement in vascular remodeling diseases has not been comprehensively studied. This study identifies a novel protein derived from a circular RNA in VSMCs and demonstrates its potential role in regulating vascular remodeling. METHODS: Cell proliferation assays were performed to investigate the effects of circSETD2(14,15 ) on VSMC proliferation. Techniques such as vector construction, immunoprecipitation–mass spectrometry, and dual-luciferase reporter gene were used to confirm that circSETD2(14,15 ) encoded a novel protein, p-414aa. The interaction between p-414aa and HuR (human antigen R) was validated with techniques such as co-immunoprecipitation, mass spectrometry, and proximity ligation assay. Through experiments including RNA sequencing and RNA immunoprecipitation, the interaction between HuR and C-FOS (C-Fos proto-oncogene) mRNA was revealed. The role of p-414aa in neointimal hyperplasia was assessed with a carotid artery ligation model in male mice. RESULTS: Overexpression of circSETD2(14,15 ) inhibits VSMC phenotypic switching. The novel protein p-414aa, encoded by circSETD2(14,15 ), interacts with HuR to reduce C-FOS mRNA stability, thereby suppressing VSMC proliferation and ultimately inhibiting neointimal hyperplasia in male mice. CONCLUSIONS: We uncover a novel hidden protein derived from circSETD2(14,15 ), called p-414aa, that inhibits vascular remodeling. CircSETD2(14,15 ) and p-414aa may serve as potential therapeutic targets for vascular remodeling diseases.
Article Details
Authors (11)
Si-Fan Wang
Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China (S.-F.W., L.-Y.Y., A.-Q.Z., Z.-Y.W., S.W., M.G., S.-G.S.).
Li-Yun Yang
Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China (S.-F.W., L.-Y.Y., A.-Q.Z., Z.-Y.W., S.W., M.G., S.-G.S.).
An-Qi Zhao
Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China (S.-F.W., L.-Y.Y., A.-Q.Z., Z.-Y.W., S.W., M.G., S.-G.S.).
Zhao-Yi Wang
Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China (S.-F.W., L.-Y.Y., A.-Q.Z., Z.-Y.W., S.W., M.G., S.-G.S.).
Sen Wang
State Key Laboratory of Coal Conversion
Miao Gong
Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China (S.-F.W., L.-Y.Y., A.-Q.Z., Z.-Y.W., S.W., M.G., S.-G.S.).
Ming-Qi Zheng
Department of Cardiology, The First Hospital of Hebei Medical University, Hebei Key Laboratory of Heart and Metabolism, Shijiazhuang, China (M.-Q.Z., G.L.).
Gang Liu
Shu-Yan Yang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China (S.-Y.Y.).
Jia-Jie Lin
School of Basic Medicine, Jiangxi Provincial Key Laboratory of Tissue Engineering, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, Gannan Medical University, Ganzhou, China (J.-J.L.).
Shao-Guang Sun
Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China (S.-F.W., L.-Y.Y., A.-Q.Z., Z.-Y.W., S.W., M.G., S.-G.S.).