miRNAs: The Key Regulator of COVID-19 Disease

Table 1

COVID-19-associated miRNAs involved in immune response.

miRNAs	Role in the immune response	miRNA expression	References
miR-15a-5p	Binding to SARS-CoV-2-encoded transcripts; Involved in immunity enhancing	Upregulated	[89, 184, 185]
miR-15b	Positively correlated with inflammation; Regulating the host immune response	Upregulated	[140, 186, 187]
miR-17-5p	Having actual target sites in SARS-CoV-2 and in inflammation response, role not well known	Downregulated	[3]
miR-21	Regulating inflammatory response; Correlated with macrophage numbers and with MCP-1 protein expression in in the bronchoalveolar lavage (BAL) supernatant; 27 binding sites on SARS-CoV-2 genome with the highest target scores	Upregulated	[80, 141, 188, 189]
miR-23a-3p	Binding to the complemented sequence which led to the recovery of the cytopathic effects; Related to cytokine–cytokine receptor interactions, TNF, NF-κB, chemokines, Toll-like receptors, and the Jak–STAT signaling pathway	Not reported	[87]
miR-25-3p	Having strong binding potential against TMPRSS2 in COVID-19 disease; Implicated in the SARS-CoV-2 talk with host cell; Downregulated in COPD	Downregulated	[74, 190–193]
miR-29a	Identified in COVID-19 infection; Anti-inflammatory in cancer and other diseases	Upregulated	[70, 139, 194]
miR-31-5p	Mediating inflammatory signaling	Downregulated	[129, 131, 140, 195]
miR-98	Negatively correlated with inflammatory cytokines	Downregulated	[196, 197]
miR-99a-5p	Targeting proinflammatory genes	Downregulated	[140, 198]
miR-124	Targeting the 3-UTR binding sites on IL-6 gene in COVID-19 disease; Suppressing LPS-induced p65 expression and cell apoptosis; Decreasing the levels of inflammation and pulmonary injury	Not reported	[199, 200]
miR-125b	Binding to the 3-UTR region of TNF and IFN and also to the 3-UTR of factor XIII gene	Downregulated	[75, 193]
miR-142-3p, miR-142-5p	Promoting inflammatory process; Downregulated in COVID-19 infection	Downregulated	[140, 188]
miR-146a-5p	Acting as biomarker and providing a molecular link between inflammation and the COVID-19 infection	Downregulated	[140, 201, 202]
miR-149-3p	Suppressing hepatic inflammatory response through antagonizing the STAT3 signaling pathway	Not reported	[1]
miR-150	Predicted to have binding sites in the SARS-CoV-2 genome; Alleviated LPS-induced inflammatory response and apoptosis; A target in the development of anti-inflammation and antiapoptosis drugs for sepsis treatment	Downregulated	[3, 63, 69, 160, 193, 203]
miR-155	Reducing proinflammatory cytokines; Increased antiviral and anti-inflammatory cytokine responses in the lungs	Upregulated	[63, 138]
miR-181a	Inhibiting secretion of proinflammatory factors especially the increase in TNF-α	Downregulated	[140, 204]
miR-195	Promoting resolution of inflammation	Upregulated	[131, 196, 205, 206]
miR-200 family	Members of this family are proinflammatory as well as anti-inflammatory; Regulating ACE2 (virus entry) in respiratory cells in COVID-19 disease	Upregulated	[207–209]
miR-320 family	Significantly correlated with CRP, IL-6, and D-dimer levels	Downregulated	[210]
miR-342-5p	Targeting N (nucleocapsid) protein gene in SARS-CoV-2 infection; Promoting inflammatory activation of macrophages		[69, 211]
miR-421	Aggravating inflammatory response in lung tissues; Identified as an ACE2 regulator; Targeting sites on 3-UTR of ACE2 in human genome	Downregulated	[53, 57, 212–215]
miR-769-3p	Attenuating the cell death, avoiding tissue damage by targeting synergistically the 3-UTR region of the TNF and IFN genes inhibiting their protein translation	Not reported	[75]
miR-1207	Derepression of its target CSF1 results in acute inflammatory response in COVID-19	Not reported	[68, 68, 213]
miR-1307	Promoting inflammatory responses; Involved in TGF-β signaling, inflammatory response, oxygen dependency, persistent wheezing, and chronic lung diseases	Downregulated	[62, 64, 213, 216]
miR-let-7	Related to inflammatory responses in COVID-19 disease especially miR-let-7b-5p and miR-let7a-5p	Downregulated	[63, 215]

Abbreviations: ACE2: angiotensin-converting enzyme 2; BAL: bronchoalveolar lavage; COPD: chronic obstructive pulmonary disease; LPS: lipopolysaccharides; TMPRSS2: transmembrane protease serine 2; STAT: signal transducer and activator of transcription 3; UTR: untranslated region.