circ-Sirt1 controls NF-B activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells
circ-Sirt1 controls NF-B activation via sequence-specific interaction and enhancement of SIRT1 expression by binding to miR-132/212 in vascular smooth muscle cells
复制标题
circ-Sirt1 通过序列特异性相互作用控制 NF-B 激活，并通过与血管平滑肌细胞中的 miR-132/212 结合增强 SIRT1 表达
DOI：
10.1093/nar/gkz141
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发表时间：
2019-04-23
影响因子：
14.9
通讯作者：
Han, Mei
中科院分区：
文献类型：
--
作者：
Kong, Peng;Yu, Yuan;Han, Mei
核因子-B介导的血管平滑肌细胞(VSMCs)的炎性表型转换在动脉粥样硬化和新生内膜形成中起核心作用。然而，对于CircRNAs在核因子-B信号调控中的作用知之甚少。在这里，我们确定了作为SIRT1宿主基因转录产物之一的CIRC-Sirt1参与了VSMC的炎症反应和新生内膜增生。首先，在细胞质中，CIRC-Sirt1以一种顺序依赖的方式直接与核因子-B p65相互作用，并从由肿瘤坏死因子-1诱导的核转位中隔离核因子-B p65。CIRC-Sirt1-NF-B p65的抑制复合体不依赖IB。第二，CIRC-Sirt1与miR-132/212结合，干扰SIRT1基因的表达，促进宿主基因SIRT1的表达。SIRT1的增加会导致核内的核因子-B p65去乙酰化和失活。这些发现说明CIRC-Sirt1是一种新的VSMC表型的非编码RNA调节因子。
NF-B-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-B 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-B p65 from nuclear translocation induced by TNF- in a sequence-dependent manner. The inhibitory complex of circ-Sirt1-NF-B p65 is not dependent on IB. 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-B p65. These findings illustrate that circ-Sirt1 is a novel non-coding RNA regulator of VSMC phenotype.