Hsa_circ_0000479/Hsa-miR-149-5p/RIG-I, IL-6 Axis: A Potential Novel Pathway to Regulate Immune Response against COVID-19

Abstract

Background. COVID-19, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic and mortality of people around the world. Some circular RNAs (circRNAs), one of the new types of noncoding RNAs (ncRNAs), act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, to regulate gene expression. In the present study, we aimed to evaluate the expression and roles of hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 in COVID-19 infection. Materials and Methods. After extraction of total RNA from peripheral blood mononuclear cells (PBMC) of 50 patients with symptomatic COVID-19, 50 patients with nonsymptomatic COVID-19, and 50 normal controls, cDNA synthesis was performed. Online in silico tools were applied to evaluate the interaction between the genes in the hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 axis, and its role in COVID-19-related pathways. Quantification of the expression of these genes and confirmation of their interaction was done using the quantitative real-time PCR (qRT-PCR) technique. Results. The expression levels of hsa_circ_0000479, RIG-I, and IL-6 were increased in COVID-19 patients compared to healthy controls, while hsa-miR-149-5p expression was decreased. Moreover, there was a significant negative correlation between hsa-miR-149-5p and hsa_circ_0000479, RIG-I, IL-6 expressions, and also a positive expression correlation between hsa_circ_0000479 and IL-6, RIG-I. Then, bioinformatics tools revealed the role of hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 axis in PI3K-AKT and STAT3 signaling pathways. Conclusion. Upregulation of hsa_circ_0000479, RIG-I, and IL-6, and downregulation of hsa-miR-149-5p, along with correlation studies, indicate that hsa_circ_0000479/hsa-miR-149-5p/RIG-I, IL-6 axis could play a role in regulating the immune response against SARS-CoV-2. However, more studies are needed in this area.

The hub genes and their potential regulatory mechanisms in chronic spontaneous urticaria revealed by integrated transcriptional expression analysis

“…33 The regulatory effect of miR-1495p on the expression of IL-6 mRNA has been widely reported in various immune-mediated inflammatory diseases, including chronic obstructive pulmonary disease, COVID-19, abdominal aortic aneurysms, ischemic stroke, osteoarthritis and rheumatoid arthritis. [34][35][36][37][38] However, the regulatory relationship between ZBTB20-AS1 and miR-149-5p is only proposed based on database prediction and has not been supported in the current literature. Up-regulation of ZBTB20-AS1 and IL-6 and their targeting by miR-149-5p, combined with findings of related studies, indicate that the ZBTB20 − AS1/miR-149-5p/IL-6 axis may play a role in CSU.…”

“…The miRNA is a noncoding RNA with a length of 19–25 nucleotides, which plays a role by blocking or degrading mRNA 33 . The regulatory effect of miR‐1495p on the expression of IL‐6 mRNA has been widely reported in various immune‐mediated inflammatory diseases, including chronic obstructive pulmonary disease, COVID‐19, abdominal aortic aneurysms, ischemic stroke, osteoarthritis and rheumatoid arthritis 34–38 . However, the regulatory relationship between ZBTB20‐AS1 and miR‐149‐5p is only proposed based on database prediction and has not been supported in the current literature.…”

Construction of atrial fibrillation‐related circRNA/lncRNA‐miRNA‐mRNA regulatory network and analysis of potential biomarkers

“…Another study on chronic obstructive pulmonary disease reported that IL6‐AS1 (lncRNA) can competitively bind to miR‐149‐5p to promote the expression of IL‐6 33 . In addition, hsa_circ_0000479‐hsa‐miR‐149‐5p‐RIG‐I and IL‐6 interaction axis play a role in COVID‐19 infection 34 . Different circRNAs / lncRNAs can act on the hsa‐miR‐149‐5p‐IL‐6 axis.…”

“…33 In addition, hsa_circ_0000479-hsa-miR-149-5p-RIG-I and IL-6 interaction axis play a role in COVID-19 infection. 34 Different cir-cRNAs / lncRNAs can act on the hsa-miR-149-5p-IL-6 axis. Our network further suggested that the upregulated FTX, circRNA_7571, may be particularly important for AF due to their roles as ceRNA F I G U R E 8 Correlation of ceRNA expression levels with differential expression binding to hsa-miR-149-5p, which leads to the upregulation of IL-6, MMP9, respectively.…”

Circular RNAs as emerging regulators in COVID-19 pathogenesis and progression

“…( 69 ) found that circRNAs composed of self-splicing introns can bind to the receptor retinoic acid-inducible gene I (RIG-I) to effectively activate immune signal transduction in the context of viral infection. A recent study also indicated that the overexpressed hsa_circ_0000479 in COVID-19 patients may regulate the expression of IL-6 and RIG-I by sponging hsa-miR-149-5p ( 55 ). Additionally, regulation of immune responses by circRNAs generally involves the transduction of signalling pathways and the production of cytokines.…”