Comprehensive network of miRNA-induced intergenic interactions and a biological role of its core in cancer.
Comprehensive network of miRNA-induced intergenic interactions and a biological role of its core in cancer.
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DOI：
10.1038/s41598-018-20215-5
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发表时间：
2018-02-05
影响因子：
4.6
通讯作者：
Tonevitsky AG
中科院分区：
文献类型：
--
作者：
Galatenko VV;Galatenko AV;Samatov TR;Turchinovich AA;Shkurnikov MY;Makarova JA;Tonevitsky AG
microRNAs（miRNAs）是一类转录后调节基因表达的非编码短RNA家族，在多种细胞过程中发挥重要作用。很大比例的miRNAs是基因内的，这通常在功能上与它们的宿主基因相关，发挥拮抗或协同作用。在这项研究中，我们构建并分析了由基因内miRNA诱导的基因间相互作用的整个网络。我们进一步关注了这个网络的核心，它被定义为非平凡强连接组件的联合，即，通过有向路径相互连接的节点（基因）集合。整个网络及其核心都具有统计上显著的非随机特性。具体而言，形成核心的基因具有高表达水平和低表达方差。此外，网络核心没有分裂成对应于单个信号传导或代谢途径的单独组件，而是整合了参与关键细胞过程的基因，包括DNA复制、转录、蛋白质稳态和细胞代谢。我们认为，网络核心，由基因内的miRNA相互调节的基因组成，可以协调相邻的通路或稳态控制电路，作为一个水平的电路间的联系。值得注意的是，这些基因的表达模式对乳腺癌和结直肠癌患者具有有效的预后潜力。
MicroRNAs (miRNAs) are a family of short noncoding RNAs that posttranscriptionally regulate gene expression and play an important role in multiple cellular processes. A significant percentage of miRNAs are intragenic, which is often functionally related to their host genes playing either antagonistic or synergistic roles. In this study, we constructed and analyzed the entire network of intergenic interactions induced by intragenic miRNAs. We further focused on the core of this network, which was defined as a union of nontrivial strongly connected components, i.e., sets of nodes (genes) mutually connected via directed paths. Both the entire network and its core possessed statistically significant non-random properties. Specifically, genes forming the core had high expression levels and low expression variance. Furthermore, the network core did not split into separate components corresponding to individual signalling or metabolic pathways, but integrated genes involved in key cellular processes, including DNA replication, transcription, protein homeostasis and cell metabolism. We suggest that the network core, consisting of genes mutually regulated by their intragenic miRNAs, could coordinate adjacent pathways or homeostatic control circuits, serving as a horizontal inter-circuit link. Notably, expression patterns of these genes had an efficient prognostic potential for breast and colorectal cancer patients.
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