Table 2.
Regulation of immune-related EV-miRNAs in COVID-19
| Circulating miRNAs | Organism/Organ/Cell type | Regulate direction | Targeted regulation | Biological effect | Reference |
|---|---|---|---|---|---|
| miR-24 | EC-EV | Downregulated in patients with cerebrovascular disorders | Targeted Neuropilin 1 | Related to cerebrovascular events and SARS-CoV-2 internalization | 179 |
| miR-92a-3p | MSC-EV | Up-regulation | Targeted the 3'UTR of SARS-CoV-2 | Blocked SARS-CoV-2 RNA replication and suppressed virus-mediated pro-inflammatory responses by human bronchial epithelial cells and lung fibroblasts | 125 |
| miR-26a-5p | MSC-EV | Up-regulation | Targeted the 3'UTR of SARS-CoV-2 | Blocked SARS-CoV-2 RNA replication and suppressed virus-mediated pro-inflammatory responses by human bronchial epithelial cells and lung fibroblasts | 125 |
| miR-23a-3p | MSC-EV | Up-regulation | Targeted the 3'UTR of SARS-CoV-2 | Blocked SARS-CoV-2 RNA replication and suppressed virus-mediated pro-inflammatory responses by human bronchial epithelial cells and lung fibroblasts | 125 |
| miR-103a-3p | MSC-EV | Up-regulation | Targeted the 3'UTR of SARS-CoV-2 | Blocked SARS-CoV-2 RNA replication and suppressed virus-mediated pro-inflammatory responses by human bronchial epithelial cells and lung fibroblasts | 125 |
| miR-181a-5p | MSC-EV | Up-regulation | Targeted the 3'UTR of SARS-CoV-2 | Blocked SARS-CoV-2 RNA replication and suppressed virus-mediated pro-inflammatory responses by human bronchial epithelial cells and lung fibroblasts | 125 |
| miR-125a-3p | MSC-EV | - | Binds to the portion 3'UTR of IL2, CXCL10, IL7, IL10 and IL15; Binds to the 3'UTR region of TNF, IFN and binds also to the 3'UTR of Factor XIII gene | Minimized cell death, alleviate the systemic inflammation and coagulation disturbs in severe COVID-19 patients improving their clinical outcome | 180 |
| miR-125b-1-3p | MSC-EV | - | Targeted the CXCL10, IL17A, IL10, CCL3, IL18 and IL33 and targeted the TNF, IFN, and GSDME genes; Binds to the 3'UTR region of Factor III, IX and XIII | Reduced inflammation | 180 |
| miR-769-3p | MSC-EV | - | Targeted synergistically the 3'UTR region of the TNF e IFN genes inhibiting their protein translation | Reduced cell death and prevented tissue damage | 180 |
| miR-202-3p | MSC-EV | - | Targeted synergistically the 3'UTR region of the TNF e IFN genes inhibiting their protein translation | Reduced cell death and prevented tissue damage | 180 |
| miR-148a | Virus-exosomal | Up-regulation | Suppress target gene expression of USP33 and downstream IRF9 levels; Regulated the major pro-inflammatory gene expression profile of TNFα, NF-κB and IFN-β | Triggered the neuroinflammation within Central Nervous System | 134 |
| miR-590 | Virus-exosomal | Up-regulation | Suppress target gene expression of USP33 and downstream IRF9 levels; Regulated the major pro-inflammatory gene expression profile of TNFα, NF-κB and IFN-β | Triggered the neuroinflammation within Central Nervous System | 134 |
| miR-7-5p | Exosomal | Downregulated in T2D patients and elderly people | Inhibited S protein expression and SARS-CoV-2 replication | Suppression of virus infection | 15 |
| miR-24-3p | Exosomal | Downregulated in T2D patients and elderly people | Inhibited S protein expression and SARS-CoV-2 replication | Suppression of virus infection | 15 |
| miR-145-5p | Exosomal | Downregulated in T2D patients and elderly people | Inhibited S protein expression and SARS-CoV-2 replication | Suppression of virus infection | 15 |
| miR-223-3p | Exosomal | Downregulated in T2D patients and elderly people | Inhibited S protein expression and SARS-CoV-2 replication | Suppression of virus infection | 15 |
| miR-21 | MSC-exosomal | Down-regulation | Reduced cytokines such as IL-7, IL-2, and IL-6 | Prevented cytokine storms | 181 |
| miR-24 | MSC-exosomal | Down-regulation | Reduced cytokines such as IL-7, IL-2, and IL-6 | Prevented cytokine storms | 181 |
| miR-124 | MSC-exosomal | Down-regulation | Reduced cytokines such as IL-7, IL-2, and IL-6 | Prevented cytokine storms | 181 |
| miR-145 | MSC-exosomal | Down-regulation | Reduced cytokines such as IL-7, IL-2, and IL-6 | Prevented cytokine storms | 181 |
| miR-146a | EV | Down-regulation | Regulated inflammation | Exhibited neutralizing activity against SARS‐CoV‐2 infection in vitro | 132 |
| miR-126-3p | EV | Down-regulation | Regulated angiogenesis | Exhibited neutralizing activity against SARS‐CoV‐2 infection in vitro | 132 |
| miR-3168 | EV | Up-regulation | Targeted IL6, OR52N2 | Regulated immune function in the pathophysiology of COVID-19 | 140 |
| miR-146a-5p | EV | Up-regulation | Targeted TLR4 | Regulated immune function in the pathophysiology of COVID-19 | 140 |
| miR-542-3p | EV | Up-regulation | Inhibited SERPINB8 and APOH | Anticoagulatory eanticoagulatory effect | 140 |
| miR-338-5p | EV | Up-regulation | Targeted IL6 and inhibited OR52N2 expression | Regulated inflammatory response and inhibited olfactory receptors | 140 |
| miR-92a-2-5p | EV | Down-regulation | Negatively correlated with degrees of adverse reactions | Expected to be associated with immune responses after vaccination with BNT162b2 | 182 |
| miR-148a | EV | Down-regulation | Associated with specific antibody titers | Expected to be associated with immune responses after vaccination with BNT162b2 | 182 |