Upregulation of hsa_circ_0004812 promotes COVID‐19 cytokine storm via hsa‐miR‐1287‐5p/IL6R, RIG‐I axis

Abstract

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.

Evaluation of the Expression of Infection-Related Long Noncoding RNAs among COVID-19 Patients: A Case-Control Study

“…Following the frst exposure of SARS-CoV-2 to the host immune system, several receptors including toll-like receptors (TLRs) and NOD-like receptors (NLRs), retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), and cyclic GMP-AMP synthase (cGAS) detect the viral particles. Afterwards, signaling cascades result in activation of innate immune responses and secretion of multiple chemokines and cytokines [6][7][8]. Some studies have shown increased levels of diferent cytokines and chemokines such as tumor necrosis factor a (TNF-α), interleukin 6 (IL-6), interleukin 7 (IL-7), C-X-C motif chemokine ligand 10 (CXCL10), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 3 (CCL3), and α-chain of IL-2 receptor [9,10].…”