A new insight into sex-specific non-coding RNAs and networks in response to SARS-CoV-2

Abstract

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.

Insights into Cardiovascular Defects and Cardiac Epigenome in the Context of COVID-19

“…Apart from histone modifications and DNA methylation, non-coding RNA (nc-RNA) is an important contributor of epigenetic changes. In COVID-19, several nc-RNA are upregulated or downregulated which render them as potential biomarkers of the disease [ 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Askari et al reported that several long nc-RNAs and micro RNAs (mi-RNAs) are differentially expressed in COVID-19, some with specific observations in female versus male patients [ 46 ].…”

“…In COVID-19, several nc-RNA are upregulated or downregulated which render them as potential biomarkers of the disease [ 46 , 47 , 48 , 49 , 50 , 51 , 52 ]. Askari et al reported that several long nc-RNAs and micro RNAs (mi-RNAs) are differentially expressed in COVID-19, some with specific observations in female versus male patients [ 46 ]. For example, comparison of female versus male COVID-19 ICU patients showed upregulation in XIST lncRNA, while downregulation in TTTY14 , TTTY10 , and ZFY-AS1 lncRNAs [ 46 ].…”

“…Askari et al reported that several long nc-RNAs and micro RNAs (mi-RNAs) are differentially expressed in COVID-19, some with specific observations in female versus male patients [ 46 ]. For example, comparison of female versus male COVID-19 ICU patients showed upregulation in XIST lncRNA, while downregulation in TTTY14 , TTTY10 , and ZFY-AS1 lncRNAs [ 46 ]. They further identified several miRNAs with multiple binding sites on SARS-CoV-2 genome, e.g., miR-29b has five binding sites.…”

“…Not only are nc-RNAs potential biomarkers, they are also important regulators. For example, miR-29a/c targets differentially expressed genes (DEGs) that are induced by COVID-19, while miR-125 and others target DEGs regulating immune response [ 46 ]. Interestingly, nc-RNAs have significant roles in cardiac biology, including miR-29s and miR-30b reported in this study, which have anti-fibrotic roles in the heart and correlate with ischemic heart disease, respectively [ 46 ].…”

“…For example, miR-29a/c targets differentially expressed genes (DEGs) that are induced by COVID-19, while miR-125 and others target DEGs regulating immune response [ 46 ]. Interestingly, nc-RNAs have significant roles in cardiac biology, including miR-29s and miR-30b reported in this study, which have anti-fibrotic roles in the heart and correlate with ischemic heart disease, respectively [ 46 ]. Badimon et al provides a comprehensive compilation of nc-RNAs, including miR-16-2-3p, lncRNA NEAT1 , which are upregulated in COVID-19 patients, and lncRNA DANCR , miR-183-5p, etc., which are downregulated [ 47 ].…”