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
| Autor: | Haijuan Hu, Fan Zhang, Yuan Yu, Mei Han, Bing-Hui Li, Yu-Tao Yong, Wei Cui, Hai-Yue Wang, Xu-Hui Zhang, Lu Wang, Yong-Qing Dou, Yabin Liu, Yan Cui, Peng Kong, Shao-Guang Sun |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Cytoplasm
Vascular smooth muscle endocrine system diseases RNA-binding protein Biology environment and public health Muscle Smooth Vascular Mice 03 medical and health sciences 0302 clinical medicine NF-KappaB Inhibitor alpha Sirtuin 1 microRNA Genetics medicine Animals Humans Molecular Biology Cell Proliferation 030304 developmental biology Inflammation Neointimal hyperplasia 0303 health sciences Messenger RNA Tumor Necrosis Factor-alpha NF-kappa B Transcription Factor RelA RNA-Binding Proteins medicine.disease NFKB1 Rats Cell biology MicroRNAs enzymes and coenzymes (carbohydrates) IκBα Gene Expression Regulation biological phenomena cell phenomena and immunity Signal transduction Carotid Artery Injuries hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|