Prediction of crucial epigenetically-associated, differentially expressed genes by integrated bioinformatics analysis and the identification of S100A9 as a novel biomarker in psoriasis
Prediction of crucial epigenetically-associated, differentially expressed genes by integrated bioinformatics analysis and the identification of S100A9 as a novel biomarker in psoriasis
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通过综合生物信息学分析预测关键的表观遗传相关差异表达基因，并将 S100A9 鉴定为银屑病的新型生物标志物
DOI：
10.3892/ijmm.2019.4392
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发表时间：
2020-01-01
影响因子：
5.4
通讯作者：
Chen, Hongxiang
中科院分区：
文献类型：
--
作者：
Wang, Xin;Liu, Xinxin;Chen, Hongxiang
银屑病是最常见的免疫介导的炎症性皮肤疾病之一。确定负责疾病发病机制的关键分子机制可能会导致新的治疗选择的发展。本研究的目的是确定关键的差异表达基因（DEGs）和甲基化的DEGs在银屑病。来自基因微阵列的原始数据从基因表达综合数据库获得。使用Bioconductor中的软件包处理数据。总共鉴定了352个上调和137个下调的DEG。上调的DEG主要富集在“先天免疫防御”反应和“细胞周期”中。下调的DEG主要集中在“细胞粘附”和“紧密连接途径”。共鉴定了95个甲基化DEG，它们显著富集在“白细胞介素（IL）-17信号通路”和“对干扰素的反应”中。在综合评价cytoHubba中所有算法的基础上，筛选出表观遗传学相关的关键hub基因（S100 A9、SELL、FCGR 3B、MMP 9、S100 A7、IL 7 R、IRF 7、CCR 7、IFI 44、CXCL 1和LCN 2）。为了进一步验证这些基因，本研究使用小鼠构建了咪喹莫特（IMQ）诱导的银屑病样皮炎模型。这些枢纽基因的水平在IMQ组中增加。在小鼠中敲低甲基化调节酶10 - 11易位（泰特）2表达可减弱S100 A9、SELL、IL 7 R、MMP 9、CXCL 1和LCN 2的表达水平。此外，S100 A9的羟甲基化水平在IMQ组中高度表达，并且在小鼠中由于TET 2缺乏而显著降低。总体而言，本研究采用系统生物信息学方法，确定了一系列特征富集途径和关键基因，可能作为银屑病的潜在生物标志物。
Psoriasis is one of the most common immune-mediated inflammatory diseases of the skin. The identification of the pivotal molecular mechanisms responsible for the disease pathogenesis may lead to the development of novel therapeutic options. The present study aimed to identify pivotal differentially expressed genes (DEGs) and methylated DEGs in psoriasis. The raw data from gene microarrays were obtained from the Gene Expression Omnibus database. The data were processed using packages in Bioconductor. In total, 352 upregulated and 137 downregulated DEGs were identified. The upregulated DEGs were primarily enriched in the 'innate immune defense' response and the 'cell cycle'. The down-regulated DEGs were primarily enriched in 'cell adhesion' and 'tight junction pathways'. A total of 95 methylated DEGs were identified, which were significantly enriched in the 'interleukin (IL)-17 signaling pathway' and the 'response to interferon'. Based on a comprehensive evaluation of all algorithms in cytoHubba, the key epigenetic-associated hub genes (S100A9, SELL, FCGR3B, MMP9, S100A7, IL7R, IRF7, CCR7, IFI44, CXCL1 and LCN2) were screened out. In order to further validate these genes, the present study constructed a model of imiquimod (IMQ)-induced psoriasiform dermatitis using mice. The levels of these hub genes were increased in the IMQ group. The knockdown of methylation-regulating enzyme ten-eleven translocation (TET) 2 expression in mice attenuated the expression levels of S100A9, SELL, IL7R, MMP9, CXCL1 and LCN2. Furthermore, the hydroxymethylated level of S100A9 was highly expressed in the IMQ group and was significantly decreased by TET2 deficiency in mice. On the whole, using an integrative system bioinformatics approach, the present study identified a series of characteristic enrichment pathways and key genes that may serve as potential biomarkers in psoriasis.