Ari Yuka Selcen, Yilmaz Alper
Department of Bioengineering, Yildiz Technical University, Istanbul, Turkey.
PeerJ. 2021 Mar 19;9:e11121. doi: 10.7717/peerj.11121. eCollection 2021.
Competing endogenous RNA (ceRNA) regulations and crosstalk between various types of non-coding RNA in humans is an important and under-explored subject. Several studies have pointed out that an alteration in miRNA:target interaction can result in unexpected changes due to indirect and complex interactions. In this article, we defined a new network-based model that incorporates miRNA:ceRNA interactions with expression values. Our approach calculates network-wide effects of perturbations in the expression level of one or more nodes in the presence or absence of miRNA interaction factors such as seed type, binding energy. We carried out the analysis of large-scale miRNA:target networks from breast cancer patients. Highly perturbing genes identified by our approach coincide with breast cancer-associated genes and miRNAs. Our network-based approach takes the sponge effect into account and helps to unveil the crosstalk between nodes in miRNA:target network. The model has potential to reveal unforeseen regulations that are only evident in the network context. Our tool is scalable and can be plugged in with emerging miRNA effectors such as circRNAs, lncRNAs, and available as R package ceRNAnetsim: https://www.bioconductor.org/packages/release/bioc/html/ceRNAnetsim.html.
人类中竞争性内源性RNA（ceRNA）调控以及各类非编码RNA之间的相互作用是一个重要且尚未充分探索的课题。多项研究指出，由于间接和复杂的相互作用，miRNA与靶标的相互作用改变可能会导致意想不到的变化。在本文中，我们定义了一种基于网络的新模型，该模型将miRNA与ceRNA的相互作用和表达值结合起来。我们的方法计算了在存在或不存在miRNA相互作用因子（如种子类型、结合能）的情况下，一个或多个节点表达水平扰动的全网络效应。我们对乳腺癌患者的大规模miRNA与靶标网络进行了分析。通过我们的方法鉴定出的高度扰动基因与乳腺癌相关基因和miRNA相吻合。我们基于网络的方法考虑了海绵效应，有助于揭示miRNA与靶标网络中节点之间的相互作用。该模型有潜力揭示仅在网络背景下才明显的意外调控。我们的工具具有可扩展性，可以与新兴的miRNA效应分子（如环状RNA、长链非编码RNA）结合使用，并且可以作为R包ceRNAnetsim获取：https://www.bioconductor.org/packages/release/bioc/html/ceRNAnetsim.html。
