Ari Yuka Selcen, Yilmaz Alper
Department of Bioengineering, Yildiz Technical University, Istanbul, Turkey.
PeerJ. 2021 Oct 20;9:e12370. doi: 10.7717/peerj.12370. eCollection 2021.
Competing endogenous RNAs (ceRNA) play a crucial role in cell functions. Computational methods that provide large-scale analysis of the interactions between miRNAs and their competitive targets can contribute to the understanding of ceRNA regulations and critical regulatory functions. Recent reports showed that viral RNAs can compete with host RNAs against host miRNAs. Regarding SARS-CoV-2 RNA, no comprehensive study had been reported about its competition with cellular ceRNAs. In this study, for the first time, we used the ceRNAnetsim package to assess ceRNA network effects per individual cell and competitive behavior of SARS-CoV-2 RNA in the infected cells using single-cell sequencing data. Our computations identified 195 genes and 29 miRNAs which vary in competitive behavior specifically in presence of SARS-CoV-2 RNA. We also investigated 18 genes that are affected by genes that lost perturbation ability in presence of SARS-CoV-2 RNA in the human miRNA:ceRNA network. These transcripts have associations with COVID-19-related symptoms as well as many dysfunctions such as metabolic diseases, carcinomas, heart failure. Our results showed that the effects of the SARS-CoV-2 genome on host ceRNA interactions and consequent dysfunctions can be explained by competition among various miRNA targets. Our perturbation ability perspective has the potential to reveal yet to be discovered SARS-CoV-2 induced effects invisible to conventional approaches.
竞争性内源性RNA（ceRNA）在细胞功能中发挥着关键作用。能够对微小RNA（miRNA）与其竞争性靶标之间的相互作用进行大规模分析的计算方法，有助于理解ceRNA调控及关键调控功能。最近的报告显示，病毒RNA可与宿主RNA竞争宿主miRNA。关于严重急性呼吸综合征冠状病毒2（SARS-CoV-2）RNA，尚未有关于其与细胞ceRNA竞争的全面研究报道。在本研究中，我们首次使用ceRNAnetsim软件包，利用单细胞测序数据评估每个细胞的ceRNA网络效应以及SARS-CoV-2 RNA在受感染细胞中的竞争行为。我们的计算确定了195个基因和29个miRNA，它们在存在SARS-CoV-2 RNA时竞争行为有所不同。我们还研究了在人类miRNA:ceRNA网络中，受SARS-CoV-2 RNA存在时失去干扰能力的基因影响的18个基因。这些转录本与2019冠状病毒病（COVID-19）相关症状以及许多功能障碍有关，如代谢疾病、癌症、心力衰竭。我们的结果表明，SARS-CoV-2基因组对宿主ceRNA相互作用及随之而来的功能障碍的影响，可以通过各种miRNA靶标之间的竞争来解释。我们从干扰能力角度出发，有可能揭示传统方法难以发现的SARS-CoV-2诱导效应。
