Regulatory Role of circRNA-۰۰۶۷۸۳۵ in Behcet Disease through Targeting Micro RNA-۱۵۵: Implication of ATG۱, 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-۱۵۵ expression. This study attempts to determine the contribution of circRNA-۰۰۶۷۸۳۵ in miRNA-۱۵۵-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 ۴۰ cases with BD and ۴۰ healthy control subjects. The collection of serum samples was done before performing a real-time PCR to estimate the relative gene expression of ATG۱, AKT, miRNA-۱۵۵, mTOR, TAB۲, and circRNA-۰۰۶۷۸۳۵. Additionally, IL-۱β, IL-۱۷, and TNF-α serum levels were determined by ELISA. Results: Behcet Disease (BD) patients had significantly upregulated circRNA-۰۰۶۷۸۳۵, with subsequent downregulation of its target gene, miRNA-۱۵۵ than controls (P<۰.۰۵). In addition, decreased miRNA-۱۵۵ gene expression was correlated with significantly increased TAB۲ gene expression levels in BD patients compared to the controls (P<۰.۰۵). Furthermore, enhanced production of pro-inflammatory cytokines was detected in cases with BD than in controls. Conclusions: The correlation between circRNA-۰۰۶۷۸۳۵ and miRNA-۱۵۵ fairly contributes to the regulation of cytokine production in BD via the modulation of autophagy. The investigation of the circRNA-۰۰۶۷۸۳۵ and the microRNA-۱۵۵ and their downstream adaptor molecules could be a potential therapeutic agent for BD.

Keywords:

Autophagy , Auto-inflammation , Behcet disease (BD) , Circular RNA-۰۰۶۷۸۰۳ , Microrna-۱۵۵.