Zhang Guanhua, Xu Zhiwen, Wang Ning
Department of Software Engineering, Jilin University, Changchun, Jilin 130012, P.R. China.
Key Laboratory of Symbol Computation and Knowledge Engineering of the Ministry of Education, Jilin University, Changchun, Jilin 130012, P.R. China.
Exp Ther Med. 2017 Jun;13(6):3039-3046. doi: 10.3892/etm.2017.4296. Epub 2017 Apr 4.
Significant progress has been made into the elucidation of the etiology of mesothelioma at the level of the genes and miRNA. Nevertheless, researchers in this field remain unable to systematically construct a network that demonstrates the specific relationships between genes, miRNA and transcription factors (TFs). TFs are key regulatory elements that control gene expression. In the present study, according to the transcriptional regulatory rule, three regulatory networks were constructed using experimentally validated elements to explore the pathogenesis of mesothelioma. We focused on the regulatory relationship between the miRNA and its host gene, the miRNA and its target gene, and the miRNA and TFs. Expressed, related and global networks were constructed, and the similarities and differences between them were analyzed. Notably, the differentially expressed network used in the present study, which was based on experimentally validated data, contained numerous incorrect expression signal pathways for the pathogenesis of mesothelioma. In theory, if these errors are corrected, this cancer may be prevented or cured. Subsequent analysis of the differentially expressed nodes and pathways may help to explain the pathogenesis of mesothelioma. Notably, some of these exhibited a self-adaption relationship, which was detected by listing the upstream and downstream elements in a table with differentially expressed genes and miRNA. The findings of the present study demonstrated detailed transcriptional regulation, which may serve as a reference to aid further elucidation of the pathogenesis of mesothelioma.
在基因和微小RNA(miRNA)层面,间皮瘤病因学的阐释已取得显著进展。然而,该领域的研究人员仍无法系统地构建一个展示基因、miRNA和转录因子(TFs)之间特定关系的网络。TFs是控制基因表达的关键调控元件。在本研究中,根据转录调控规则,利用经过实验验证的元件构建了三个调控网络,以探究间皮瘤的发病机制。我们重点关注miRNA与其宿主基因、miRNA与其靶基因以及miRNA与TFs之间的调控关系。构建了表达网络、相关网络和全局网络,并分析了它们之间的异同。值得注意的是,本研究中使用的差异表达网络基于经过实验验证的数据,其中包含许多关于间皮瘤发病机制的错误表达信号通路。从理论上讲,如果纠正这些错误,这种癌症可能会被预防或治愈。对差异表达节点和通路的后续分析可能有助于解释间皮瘤的发病机制。值得注意的是,其中一些表现出一种自适应关系,这是通过在包含差异表达基因和miRNA的表格中列出上游和下游元件检测到的。本研究结果展示了详细的转录调控,可为进一步阐明间皮瘤的发病机制提供参考。