GDPD5 Immune Inflammation-Mediated Angiogenesis and Invasion Regulation Network in Human Hepatocellular Carcinoma (HCC) by Biocomputation
首发时间:2018-11-19
Abstract:We data-analyzed and constructed the high-expression GDPD5 immune inflammation-mediated angiogenesis and invasion regulation network in human hepatocellular carcinoma (HCC) compared with low-expression (fold change≥2) no-tumor hepatitis/cirrhotic tissues (HBV or HCV infection) in GEO data set, by using integration of gene regulatory network inference method with gene ontology (GO). Our result showed that GDPD5 immune inflammation and multi-regulation upstream network BIRC5, BRCA1, CDKN3, EYA1, HOXD4, LEF1, PLA2G1B, PROK1, PTHLH, ROBO1, SCML2, REG3A activated GDPD5, and downstream GDPD5-activated CAD, CDC2, CDKN3, DKK1, E2F1, FOXM1, HMGB2, MAP2, MYCN, MYH6, NEK2, NR5A1, PROK1 in HCC. We proposed that GDPD5 activated network enhanced blood coagulation, chemotaxis, inflammatory response, interleukin-8 production, leukocyte migration, neutrophil chemotaxis, neutrophil mediated immunity, receptor mediated endocytosis, positive regulation of DNA repair, positive regulation of protein ubiquitination, as a result of inducing immune inflammation-mediated angiogenesis and invasion regulation in HCC. Our hypothesis was verified by GDPD5 regulation subnetwork containing angiogenesis, cell proliferation, transcription from RNA polymerase II promoter, transcription from RNA polymerase III promoter, Wnt receptor signaling pathway; also by GDPD5 negative regulation subnetwork including centriole replication, fatty acid biosynthesis, transcription, cell-cell adhesion, microtubule depolymerization in HCC, respectively.
keywords: GDPD5 human hepatocellular carcinoma (HCC) immune inflammation-mediated angiogenesis and invasion regulation network biocomputation
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基于生物计算的GDPD5在肝癌中免疫炎症介导的血管新生和侵润调节网络
摘要:本文利用GEO数据集,通过整合基因调控网络推理方法与基因本体论(GO),比较低表达无肿瘤肝炎及肝硬化组织(HBV或HCV感染),数据分析和构建了高表达肝癌中GDPD5的免疫炎症介导的血管新生和侵润调节网络。GDPD5的免疫炎症和多种调节网络结果表明:在肝癌中,上游BIRC5、BRCA1、CDKN3、EYA1、HOXD4、LEF1、PLA2G1B、PROK1、PTHLH、ROBO1、SCML2、REG3A激活GDPD5;并且下游GDPD5激活CAD、CDC2、CDKN3、DKK1、E2F1、FOXM1、HMGB2、MAP2、MYCN、MYH6、NEK2、NR5A1、PROK1。我们推断肝癌中GDPD5激活网络增强了血液凝固,趋化性,炎症反应,白细胞介素-8生产,白细胞迁移,中性粒细胞的趋化,中性粒细胞介导的免疫,受体介导的内吞作用,DNA修复正调节,泛素化蛋白的正调节,从而诱导免疫炎症介导的血管新生和侵润调节。进一步验证提出的假说分别通过肝癌中的GDPD5调节子网络包括调节血管新生,细胞增殖,RNA聚合酶II启动子的转录,RNA聚合酶III启动子的转录,Wnt受体信号通路;以及肝癌中的GDPD5负调节子网络含有中心粒复制,脂肪酸生物合成,转录,细胞-细胞粘附,微管解聚。
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基于生物计算的GDPD5在肝癌中免疫炎症介导的血管新生和侵润调节网络
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