Transcriptional Profiling of Hypoxia-Regulated Non-coding RNAs in Human Primary Endothelial Cells.
Transcriptional Profiling of Hypoxia-Regulated Non-coding RNAs in Human Primary Endothelial Cells.
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DOI：
10.3389/fcvm.2018.00159
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发表时间：
2018
影响因子：
3.6
通讯作者：
Kaikkonen MU
中科院分区：
文献类型：
--
作者：
Moreau PR;Örd T;Downes NL;Niskanen H;Bouvy-Liivrand M;Aavik E;Ylä-Herttuala S;Kaikkonen MU
缺氧发生在人体动脉粥样硬化病变中，对内皮细胞代谢产生多种不利影响。最近，长链非编码RNA（lncRNA）在动脉粥样硬化发展中的关键作用已经开始显现。在这项研究中，我们使用全局连续测序（GRO-Seq）研究了缺氧的人脐静脉内皮细胞的lncRNA谱。我们证明缺氧调节约 1800 个 lncRNA 的新生转录。有趣的是，我们发现证据表明，与增强子相关的lncRNA相比，启动子相关的lncRNA更容易被缺氧诱导，而增强子相关的lncRNA表现出上调和下调转录本的均匀分布。我们还证明，缺氧会导致转录因子和其他与血管生成、细胞存活和粘附有关的基因旁边的超级增强子的活性显着诱导，而血管生成的几个负调节因子附近的超级增强子则受到抑制。尽管大多数 lncRNA 在 RNA-Seq 中表现出较低的检测率，但一部分 lncRNA 的表达水平与 mRNA 相当。其中，与正常血管组织相比，MALAT1、HYMAI、LOC730101、KIAA1656 和 LOC339803 在人类动脉粥样硬化病变中存在差异表达，因此可能作为病变缺氧的潜在生物标志物。
Hypoxia occurs in human atherosclerotic lesions and has multiple adverse effects on endothelial cell metabolism. Recently, key roles of long non-coding RNAs (lncRNAs) in the development of atherosclerosis have begun to emerge. In this study, we investigate the lncRNA profiles of human umbilical vein endothelial cells subjected to hypoxia using global run-on sequencing (GRO-Seq). We demonstrate that hypoxia regulates the nascent transcription of ~1800 lncRNAs. Interestingly, we uncover evidence that promoter-associated lncRNAs are more likely to be induced by hypoxia compared to enhancer-associated lncRNAs, which exhibit an equal distribution of up- and downregulated transcripts. We also demonstrate that hypoxia leads to a significant induction in the activity of super-enhancers next to transcription factors and other genes implicated in angiogenesis, cell survival and adhesion, whereas super-enhancers near several negative regulators of angiogenesis were repressed. Despite the majority of lncRNAs exhibiting low detection in RNA-Seq, a subset of lncRNAs were expressed at comparable levels to mRNAs. Among these, MALAT1, HYMAI, LOC730101, KIAA1656, and LOC339803 were found differentially expressed in human atherosclerotic lesions, compared to normal vascular tissue, and may thus serve as potential biomarkers for lesion hypoxia.
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影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
48
作者：
Diao Y;Fang R;Li B;Meng Z;Yu J;Qiu Y;Lin KC;Huang H;Liu T;Marina RJ;Jung I;Shen Y;Guan KL;Ren B
通讯作者：
Ren B
影响因子：
12.4
作者：
Downes, Nicholas L.;Laham-Karam, Nihay;Yla-Herttuala, Seppo
通讯作者：
Yla-Herttuala, Seppo
影响因子：
10.5
作者：
Henriques T;Scruggs BS;Inouye MO;Muse GW;Williams LH;Burkholder AB;Lavender CA;Fargo DC;Adelman K
通讯作者：
Adelman K
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK