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Identification of epigenetically altered genes and potential gene targets in melanoma using bioinformatic methods

机译:使用生物信息学方法鉴定黑色素瘤的表观遗传改变的基因和潜在的基因靶标

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摘要

This study aimed to analyze epigenetically and genetically altered genes in melanoma to get a better understanding of the molecular circuitry of melanoma and identify potential gene targets for the treatment of melanoma. The microarray data of , including mRNA expression profiles (seven melanoma and four melanocyte samples) and DNA methylation profiles (seven melanoma and five melanocyte samples), were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated positions (DMPs) were screened using the linear models for microarray data (limma) package in melanoma compared with melanocyte samples. Gene ontology (GO) and pathway enrichment analysis of the DEGs were carried out using the Database for Annotation, Visualization, and Integrated Discovery. Moreover, differentially methylated genes (DMGs) were identified, and a transcriptional regulatory network was constructed using the University of California Santa Cruz genome browser database. A total of 1,215 DEGs (199 upregulated and 1,016 downregulated) and 14,094 DMPs (10,450 upregulated and 3,644 downregulated) were identified in melanoma compared with melanocyte samples. Additionally, the upregulated and downregulated DEGs were significantly associated with different GO terms and pathways, such as pigment cell differentiation, biosynthesis, and metabolism. Furthermore, the transcriptional regulatory network showed that DMGs such as Aristaless-related homeobox (ARX), damage-specific DNA binding protein 2 (DDB2), and myelin basic protein (MBP) had higher node degrees. Our results showed that several methylated genes (ARX, DDB2, and MBP) may be involved in melanoma progression.
机译:这项研究旨在分析黑色素瘤的表观遗传和遗传改变的基因,以更好地了解黑色素瘤的分子回路,并确定治疗黑色素瘤的潜在基因靶标。从Gene Expression Omnibus数据库下载了mRNA的微阵列数据,包括mRNA表达谱(七个黑素瘤和四个黑素细胞样本)和DNA甲基化谱(七个黑素瘤和五个黑素细胞样本)。与黑色素细胞样品相比,使用线性模型筛选黑色素瘤中微阵列数据(limma)数据包的差异表达基因(DEGs)和差异甲基化位置(DMPs)。使用注释,可视化和集成发现数据库进行了DEG的基因本体(GO)和途径富集分析。此外,鉴定出差异甲基化基因(DMG),并使用加利福尼亚大学圣克鲁斯大学基因组浏览器数据库构建了转录调控网络。与黑色素细胞样本相比,在黑色素瘤中总共鉴定出1,215个DEG(199个上调和1,016个下调)和14,094个DMP(10,450个上调和3,644个下调)。此外,DEG的上调和下调与不同的GO术语和途径显着相关,例如色素细胞分化,生物合成和代谢。此外,转录调控网络表明,DMG(如无Aristaless相关同源盒(ARX),损伤特异性DNA结合蛋白2(DDB2)和髓鞘碱性蛋白(MBP))具有更高的节点度。我们的结果表明,一些甲基化基因(ARX,DDB2和MBP)可能与黑色素瘤的进展有关。

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