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. Issue 7 (1st March 2019)

• Record Type: Journal Article
• Authors: Kong, Peng; Yu, Yuan; Wang, Lu; Dou, Yong-Qing; Zhang, Xu-Hui; Cui, Yan; Wang, Hai-Yue; Yong, Yu-Tao; Liu, Ya-Bin; Hu, Hai-Juan; Cui, Wei; Sun, Shao-Guang; Li, Bing-Hui; Zhang, Fan; Han, Mei
• Is Part Of: Nucleic acids research. Volume 47:Issue 7(2019)
• Page Start: 3580
• Page End: 3593
• Publication Date: 2019-03-01
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkz141
• Languages: English
• ISSNs: 0305-1048

Abstract

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.