Department of Biotechnology, Institute of Sciences and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran.
Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
Infect Genet Evol. 2022 Jan;97:105195. doi: 10.1016/j.meegid.2021.105195. Epub 2021 Dec 23.
SARS-CoV-2 is the RNA virus responsible for COVID-19, the prognosis of which has been found to be slightly worse in men. The present study aimed to analyze the expression of different mRNAs and their regulatory molecules (miRNAs and lncRNAs) to consider the potential existence of sex-specific expression patterns and COVID-19 susceptibility using bioinformatics analysis. The binding sites of all human mature miRNA sequences on the SARS-CoV-2 genome nucleotide sequence were predicted by the miRanda tool. Sequencing data was excavated using the Galaxy web server from GSE157103, and the output of feature counts was analyzed using DEseq2 packages to obtain differentially expressed genes (DEGs). Gene set enrichment analysis (GSEA) and DEG annotation analyses were performed using the ToppGene and Metascape tools. Using the RNA Interactome Database, we predicted interactions between differentially expressed lncRNAs and differentially expressed mRNAs. Finally, their networks were constructed with top miRNAs. We identified 11 miRNAs with three to five binding sites on the SARS-COVID-2 genome reference. MiR-29c-3p, miR-21-3p, and miR-6838-5p occupied four binding sites, and miR-29a-3p had five binding sites on the SARS-CoV-2 genome. Moreover, miR-29a-3p, and miR-29c-3p were the top miRNAs targeting DEGs. The expression levels of miRNAs (125, 181b, 130a, 29a, b, c, 212, 181a, 133a) changed in males with COVID-19, in whom they regulated ACE2 expression and affected the immune response by affecting phagosomes, complement activation, and cell-matrix adhesion. Our results indicated that XIST lncRNA was up-regulated, and TTTY14, TTTY10, and ZFY-AS1 lncRN as were down-regulated in both ICU and non-ICU men with COVID-19. Dysregulation of noncoding-RNAs has critical effects on the pathophysiology of men with COVID-19, which is why they may be used as biomarkers and therapeutic agents. Overall, our results indicated that the miR-29 family target regulation patterns and might become promising biomarkers for severity and survival outcome in men with COVID-19.
SARS-CoV-2 是导致 COVID-19 的 RNA 病毒，据发现，男性 COVID-19 的预后稍差。本研究旨在通过生物信息学分析，分析不同 mRNA 及其调节分子（miRNA 和 lncRNA）的表达，以考虑是否存在潜在的性别特异性表达模式和 COVID-19 易感性。使用 miRanda 工具预测所有人类成熟 miRNA 序列在 SARS-CoV-2 基因组核苷酸序列上的结合位点。使用 Galaxy 网络服务器从 GSE157103 挖掘测序数据，使用 DEseq2 包分析特征计数的输出，以获得差异表达基因（DEGs）。使用 ToppGene 和 Metascape 工具进行基因集富集分析（GSEA）和 DEG 注释分析。使用 RNA 相互作用数据库，预测差异表达 lncRNA 和差异表达 mRNA 之间的相互作用。最后，用 top miRNAs 构建它们的网络。我们在 SARS-COVID-2 基因组参考中发现了 11 个具有三个到五个结合位点的 miRNA。miR-29c-3p、miR-21-3p 和 miR-6838-5p 占据四个结合位点，而 miR-29a-3p 在 SARS-CoV-2 基因组上有五个结合位点。此外，miR-29a-3p 和 miR-29c-3p 是靶向 DEGs 的顶级 miRNA。在患有 COVID-19 的男性中，miRNAs（125、181b、130a、29a、b、c、212、181a、133a）的表达水平发生了变化，它们通过调节 ACE2 表达并影响吞噬体、补体激活和细胞-基质粘附来影响免疫反应。我们的结果表明，XIST lncRNA 在 ICU 和非 ICU 男性 COVID-19 患者中上调，TTTY14、TTTY10 和 ZFY-AS1 lncRNA 下调。非编码 RNA 的失调对男性 COVID-19 的病理生理学有重要影响，因此它们可能被用作生物标志物和治疗剂。总的来说，我们的结果表明，miR-29 家族的靶标调节模式可能成为男性 COVID-19 严重程度和生存结局的有前途的生物标志物。
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