Hashemi Sheikhshabani Somayeh, Amini-Farsani Zeinab, Modarres Parastoo, Amini-Farsani Zahra, Khazaei Feyzabad Sharareh, Shaygan Nasibeh, Hussen Bashdar Mahmud, Omrani Mir Davood, Ghafouri-Fard Soudeh
Student Research Committee, Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Hum Gene (Amst). 2023 May;36:201172. doi: 10.1016/j.humgen.2023.201172. Epub 2023 Apr 11.
COVID-19 has been found to affect the expression profile of several mRNAs and miRNAs, leading to dysregulation of a number of signaling pathways, particularly those related to inflammatory responses. In the current study, a systematic biology procedure was used for the analysis of high-throughput expression data from blood specimens of COVID-19 and healthy individuals. Differentially expressed miRNAs in blood specimens of COVID-19 vs. healthy specimens were then identified to construct and analyze miRNA-mRNA networks and predict key miRNAs and genes in inflammatory pathways. Our results showed that 171 miRNAs were expressed as outliers in box plot and located in the critical areas according to our statistical analysis. Among them, 8 miRNAs, namely miR-1275, miR-4429, miR-4489, miR-6721-5p, miR-5010-5p, miR-7110-5p, miR-6804-5p and miR-6881-3p were found to affect expression of key genes in NF-KB, JAK/STAT and MAPK signaling pathways implicated in COVID-19 pathogenesis. In addition, our results predicted that 25 genes involved in above-mentioned inflammatory pathways were targeted not only by these 8 miRNAs but also by other obtained miRNAs (163 miRNAs). The results of the current in silico study represent candidate targets for further studies in COVID-19.
研究发现，新冠病毒（COVID-19）会影响多种信使核糖核酸（mRNA）和微小核糖核酸（miRNA）的表达谱，导致一些信号通路失调，尤其是与炎症反应相关的信号通路。在本研究中，我们采用系统生物学方法分析了COVID-19患者和健康个体血液样本的高通量表达数据。随后，我们鉴定了COVID-19血液样本与健康样本中差异表达的miRNA，以构建和分析miRNA-mRNA网络，并预测炎症通路中的关键miRNA和基因。我们的结果显示，根据统计分析，171种miRNA在箱线图中表现为异常值，并位于关键区域。其中，发现8种miRNA，即miR-1275、miR-4429、miR-4489、miR-6721-5p、miR-5010-5p、miR-7110-5p、miR-6804-5p和miR-6881-3p，会影响参与COVID-19发病机制的核因子-κB（NF-κB）、Janus激酶/信号转导和转录激活因子（JAK/STAT）以及丝裂原活化蛋白激酶（MAPK）信号通路中关键基因的表达。此外，我们的结果预测，参与上述炎症通路的25个基因不仅受到这8种miRNA的靶向作用，还受到其他获得的miRNA（163种miRNA）的靶向作用。当前计算机模拟研究的结果代表了COVID-19进一步研究的候选靶点。
