Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.
Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.
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编码和非编码基因调控网络是肝硬化免疫反应的基础。
DOI：
10.1371/journal.pone.0174142
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Xue D
中科院分区：
文献类型：
--
作者：
Gao B;Zhang X;Huang Y;Yang Z;Zhang Y;Zhang W;Gao ZH;Xue D
肝硬化被认为是免疫介导的肝细胞损伤和修复过程的结果。然而，这些免疫反应的调节肝硬化的基础尚未阐明。在本研究中，我们使用GEO数据集和生物信息学方法建立了编码和非编码基因调控网络，包括转录因子-/lncRNA-microRNA-mRNA，以及竞争性内源RNA相互作用网络。结果发现2224个mRNA、70个lncRNA和46个microRNA在肝硬化组织中有差异表达。我们发现的导致免疫介导的肝硬化的转录因子-/lncRNA-microRNA-mRNA网络由5个核心microRNA组成（例如，miR-203; miR-219- 5 p），3种转录因子（即，FOXP 3、ETS 1和FOS）和7种lncRNA（例如，ENTS00000671336，ENST00000575137）。我们发现的竞争性内源性RNA相互作用网络包括一个复杂的免疫反应调节子网络，它控制着整个肝硬化网络。此外，我们还发现了肝硬化和肝细胞癌共有的10个重叠GO术语，包括“免疫反应”。有趣的是，肝硬化和肝细胞癌中重叠的差异表达基因在免疫应答相关的功能术语中富集。总之，免疫应答过程中的复杂基因调控网络可能在肝硬化的发展和进展中发挥重要作用，并发展为肝细胞癌。
Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including “immune response” as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.