Regulatory Role of circRNA-0067835 in Behcet Disease through Targeting Micro RNA-155: Implication of ATG1, AKT and MTOR

Background: Autophagy has been proven to contribute to maintaining eukaryotic cells' normal intracellular homeostasis, whereas autophagy malfunction may predispose to Behcet Disease (BD). The accumulation of the products of autophagic degradation as well as impairment in autophagic flux in cases with BD, may be attributed to dysregulated miRNA-155 expression. This study attempts to determine the contribution of circRNA-0067835 in miRNA-155-mediated modulation of the autophagy axis as well as to investigate its impact on the production of pro-inflammatory cytokines in BD.

Methods: This study was carried out on 40 cases with BD and 40 healthy control subjects. The collection of serum samples was done before performing a real-time PCR to estimate the relative gene expression of ATG1, AKT, miRNA-155, mTOR, TAB2, and circRNA-0067835. Additionally, IL-1β, IL-17, and TNF-α serum levels were determined by ELISA.

Results: Behcet Disease (BD) patients had significantly upregulated circRNA-0067835, with subsequent downregulation of its target gene, miRNA-155 than controls (P<0.05). In addition, decreased miRNA-155 gene expression was correlated with significantly increased TAB2 gene expression levels in BD patients compared to the controls (P<0.05). Furthermore, enhanced production of pro-inflammatory cytokines was detected in cases with BD than in controls.

Conclusion: The correlation between circRNA-0067835 and miRNA-155 fairly contributes to the regulation of cytokine production in BD via the modulation of autophagy. The investigation of the circRNA-0067835 and the microRNA-155 and their downstream adaptor molecules could be a potential therapeutic agent for BD.