Huang Tse-Shun, Wang Kuei-Chun, Quon Sara, Nguyen Phu, Chang Ting-Yu, Chen Zhen, Li Yi-Shuan, Subramaniam Shankar, Shyy John, Chien Shu
Institute of Engineering in Medicine, University of California, San Diego, La Jolla, California.
College of Medical Science and Technology, Taipei Medical University, Taiwan.
Physiol Genomics. 2017 Jul 1;49(7):339-345. doi: 10.1152/physiolgenomics.00132.2016. Epub 2017 May 12.
The long noncoding RNAs (lncRNAs), which constitute a large portion of the transcriptome, have gained intense research interest because of their roles in regulating physiological and pathophysiological functions in the cell. We identified from RNA-Seq profiling a set of lncRNAs in cultured human umbilical vein endothelial cells (HUVECs) that are differentially regulated by atheroprotective vs. atheroprone shear flows. Among the comprehensively annotated lncRNAs, including both known and novel transcripts, LINC00341 is one of the most abundant lncRNAs in endothelial cells. Moreover, its expression level is enhanced by atheroprotective pulsatile shear flow and atorvastatin. Overexpression of LINC00341 suppresses the expression of vascular cell adhesion molecule 1 (VCAM1) and the adhesion of monocytes induced by atheroprone flow and tumor necrosis factor-alpha. Underlying this anti-inflammatory role, LINC00341 guides enhancer of zest homolog 2, a core histone methyltransferase of polycomb repressive complex 2, to the promoter region of the gene to suppress VCAM1. Network analysis reveals that the key signaling pathways (e.g., Rho and PI3K/AKT) are co-regulated with LINC00341 in endothelial cells in response to pulsatile shear. Together, these findings suggest that LINC00341, as an example of lncRNAs, plays important roles in modulating endothelial function in health and disease.
长链非编码RNA（lncRNAs）构成了转录组的很大一部分，因其在调节细胞生理和病理生理功能中的作用而引起了广泛的研究兴趣。我们通过RNA测序分析在培养的人脐静脉内皮细胞（HUVECs）中鉴定出一组lncRNAs，它们在抗动脉粥样硬化剪切流与促动脉粥样硬化剪切流的作用下受到不同程度的调节。在全面注释的lncRNAs中，包括已知和新的转录本，LINC00341是内皮细胞中最丰富的lncRNAs之一。此外，其表达水平在抗动脉粥样硬化的脉动剪切流和阿托伐他汀的作用下增强。LINC00341的过表达抑制了血管细胞粘附分子1（VCAM1）的表达以及促动脉粥样硬化流和肿瘤坏死因子-α诱导的单核细胞粘附。LINC00341发挥这种抗炎作用的机制是，它将多梳抑制复合物2的核心组蛋白甲基转移酶——zest同源物2增强子引导至该基因的启动子区域，从而抑制VCAM1。网络分析表明，关键信号通路（如Rho和PI3K/AKT）在脉动剪切作用下与内皮细胞中的LINC00341共同受到调节。总之，这些发现表明，作为lncRNAs的一个例子，LINC00341在调节健康和疾病状态下的内皮功能中发挥着重要作用。
