1. circ-Sirt1 controls NF-κB activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells.
- Author
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Kong P, Yu Y, Wang L, Dou YQ, Zhang XH, Cui Y, Wang HY, Yong YT, Liu YB, Hu HJ, Cui W, Sun SG, Li BH, Zhang F, and Han M
- Subjects
- Animals, Carotid Artery Injuries genetics, Carotid Artery Injuries pathology, Cell Proliferation genetics, Cytoplasm genetics, Gene Expression Regulation genetics, Humans, Inflammation genetics, Inflammation pathology, Mice, Muscle, Smooth, Vascular pathology, NF-KappaB Inhibitor alpha genetics, NF-kappa B genetics, RNA-Binding Proteins, Rats, Signal Transduction, Transcription Factor RelA genetics, Tumor Necrosis Factor-alpha genetics, MicroRNAs genetics, MicroRNAs metabolism, Muscle, Smooth, Vascular metabolism, Sirtuin 1 genetics
- Abstract
NF-κB-mediated inflammatory phenotypic switching of vascular smooth muscle cells (VSMCs) plays a central role in atherosclerosis and neointimal formation. However, little is known about the roles of circRNAs in the regulation of NF-κB signaling. Here, we identify the involvement of circ-Sirt1 that was one of transcripts of SIRT1 host gene in VSMC inflammatory response and neointimal hyperplasia. First, in the cytoplasm, circ-Sirt1 directly interacts with and sequesters NF-κB p65 from nuclear translocation induced by TNF-α in a sequence-dependent manner. The inhibitory complex of circ-Sirt1-NF-κB p65 is not dependent on IκBα. Second, circ-Sirt1 binds to miR-132/212 that interferes with SIRT1 mRNA, and facilitates the expression of host gene SIRT1. Increased SIRT1 results in deacetylation and inactivation of the nuclear NF-κB p65. These findings illustrate that circ-Sirt1 is a novel non-coding RNA regulator of VSMC phenotype., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2019
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