Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells.
Identification of Differently Expressed mRNAs in Atherosclerosis Reveals CDK6 Is Regulated by circHIPK3/miR-637 Axis and Promotes Cell Growth in Human Vascular Smooth Muscle Cells.
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DOI：
10.3389/fgene.2021.596169
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发表时间：
2021
影响因子：
3.7
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Kang L;Jia H;Huang B;Lu S;Chen Z;Shen J;Zou Y;Wang C;Sun Y
动脉粥样硬化是心脏病和中风的主要原因，也是全球死亡和残疾的主要原因之一。血管平滑肌细胞的表型转化在动脉粥样硬化的病理过程中起着重要作用。本研究旨在通过分析GSE6088数据库来鉴定动脉粥样硬化中差异表达的mRNAs。结果显示，动脉粥样硬化的差异表达基因共有467个增加，490个减少。生物信息学分析表明，DEGS大量存在于乙醛和二羧酸代谢、酪氨酸代谢、色氨酸代谢、β-丙氨酸代谢、脂肪酸生物合成以及淀粉和蔗糖代谢等途径中。接下来，我们构建了一个蛋白质-蛋白质相互作用(PPI)网络来识别动脉粥样硬化中的HUB基因。此外，我们发现CDK6是动脉粥样硬化的关键调节因子。在本研究中，我们发现CDK6基因下调抑制了HASMC和HUASMC细胞的增殖。环状RNA(CircRNA，CircRNA)是一种非编码的RNA，近年来被报道对肿瘤的发生过程等方面产生了不寻常的影响。以前的研究表明，CircRNAs可以作为miRNAs在多种生物过程中海绵。生物信息学预测和荧光素酶分析表明，CDK6受CircHIPK3/miR-637靶向调控。此外，沉默HIPK3基因还可显著诱导细胞周期停滞和凋亡。综上所述，本研究通过影响miR-637/CDK6轴，发现了CircHIPK3在VSMCs增殖和凋亡中的重要调控作用。
Atherosclerosis is the leading cause of heart disease and stroke, and one of the leading causes of death and disability worldwide. The phenotypic transformation of vascular smooth muscle cells (VSMCs) plays an important role in the pathological process of atherosclerosis. The present study aimed to identify differently expressed mRNAs in atherosclerosis by analyzing GSE6088 database. Our results revealed there were totally 467 increased and 490 decreased differential expressed genes (DEGs) in atherosclerosis. Bioinformatics analysis demonstrated that the DEGs substantially existed in pathways, including Glyoxylate and dicarboxylate metabolism, Tyrosine metabolism, Tryptophan metabolism, Beta-Alanine metabolism, Fatty acid biosynthesis and Starch and sucrose metabolism. Next, we constructed a protein-protein interaction (PPI) network to identify hub genes in atherosclerosis. Also, we identified CDK6 as a key regulator of atherosclerosis. In this study, we found that CDK6 knockdown suppressed HASMC and HUASMC cell proliferation. Circular RNA (CircRNA) is a non-coding RNA which is reported to have an unusual influence on tumorigenesis process and other aspects in the last few years. Previous studies showed circRNAs could act as miRNAs sponging in multiple biological processes. Bioinformatics prediction and luciferase analysis showed that CDK6 were targeted and regulated by circHIPK3/miR-637. Moreover, silencing circHIPK3 could also significantly induce the arrest and apoptosis of cell cycle. In conclusion, this study discovered the important regulatory role of circHIPK3 in the proliferation and apoptosis of VSMCs by influencing the miR-637/CDK6 axis.