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

Nucleic Acids Research
Peng KongMei Han

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.

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Citations

May 19, 2020·Journal of Clinical Laboratory Analysis·Yezhao WangJunming Guo
May 6, 2020·The FEBS Journal·Eithne Margaret Maguire, Qingzhong Xiao
Jun 5, 2020·American Journal of Hypertension·Fred S LambRyan J Stark
Nov 16, 2020·Life Sciences·Yuchan YuanPeng Qu
Jan 12, 2021·Molecular Therapy. Nucleic Acids·Tong ShaoXing-Dong Xiong
Mar 6, 2021·Molecular Therapy. Nucleic Acids·Xi YangYonghong Li
Mar 13, 2021·Frontiers in Cardiovascular Medicine·Ruoran LinShijie Xin
May 26, 2020·Life Sciences·Qidong CaoChunli Song
Mar 14, 2021·Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics·Yu ZhangMingyou Li
Apr 17, 2021·Oxidative Medicine and Cellular Longevity·Pin LvMei Han
Jul 27, 2021·Oxidative Medicine and Cellular Longevity·Yanshuo HanJian Zhang
Jul 25, 2021·Vascular Pharmacology·Xueyuan SunLijuan Huang
Sep 22, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Haoyu SongJianping Bin
Aug 24, 2019·Experimental and Molecular Pathology·Shengwei ShiDeguang Wu
Nov 9, 2021·Frontiers in Genetics·Pengpeng ZhangYongjie Xu
Nov 20, 2021·Frontiers in Cardiovascular Medicine·Baohui YuanLi-Long Pan

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Methods Mentioned

BETA
nuclear translocation
dissection
PCR
Transfection
reverse transcription-PCR
PCRs
co-immunoprecipitation
immunoprecipitation assay
pull-down
immunoprecipitation

Software Mentioned

Graphpad Prism
Image Pro Plus
LAS AF Lite
GraphPad
TargetScan
catRAPID
miRanda
PITA
RNAhybrid

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