RESUMEN
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.
RESUMEN
BACKGROUND: SARS-CoV-2 is one of the most contagious viruses in the Coronaviridae (CoV) family, which has become a pandemic. The aim of this study is to understand more about the role of hsa_circ_0004812 in the SARS-CoV-2 related cytokine storm and its associated molecular mechanisms. MATERIALS AND METHODS: cDNA synthesis was performed after total RNA was extracted from the peripheral blood mononuclear cells (PBMC) of 46 patients with symptomatic COVID-19, 46 patients with asymptomatic COVID-19, and 46 healthy controls. The expression levels of hsa_circ_0004812, hsa-miR-1287-5p, IL6R, and RIG-I were determined using qRT-PCR, and the potential interaction between these molecules was confirmed by bioinformatics tools and correlation analysis. RESULTS: hsa_circ_0004812, IL6R, and RIG-I are expressed higher in the severe symptom group compared with the negative control group. Also, the relative expression of these genes in the asymptomatic group is lower than in the severe symptom group. The expression level of hsa-miR-1287-5p was positively correlated with symptoms in patients. The results of the bioinformatics analysis predicted the sponging effect of hsa_circ_0004812 as a competing endogenous RNA on hsa-miR-1287-5p. Moreover, there was a significant positive correlation between hsa_circ_0004812, RIG-I, and IL-6R expressions, and also a negative expression correlation between hsa_circ_0004812 and hsa-miR-1287-5p and between hsa-miR-1287-5p, RIG-I, and IL-6R. CONCLUSION: The results of this in-vitro and in silico study show that hsa_circ_0004812/hsa-miR-1287-5p/IL6R, RIG-I can play an important role in the outcome of COVID-19.