Circ_0082476 targets miR-138-5p to promote proliferation, invasion, migration and inflammation in IL-22-treated human keratinocytes by upregulating BRD4

Background: Circular RNAs (circRNAs) are implicated in the disease progression via acting as sponges of microRNAs (miRNAs) to regulate gene expression. The purpose of this study was to analyze the involvement of circ_0082476 in Interleukin-22 (IL-22)-induced psoriasis.

Methods: Expression detection for circ_0082476, microRNA-424-5p (miR-138-5p) or toll-like receptor (BRD4) was completed using reverse transcription-quantitative polymerase chain reaction assay. Cell Counting Kit-8 assay and EdU assay were used for analysis of cell viability and proliferation, respectively. Cell invasion and migration abilities were assessed through transwell assay and wound healing assay. The protein expression was examined via western blot. Inflammatory reaction was determined via Enzyme-linked immunosorbent assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted for target binding research.

Results: Circ_0082476 was significantly elevated in psoriasis patients and IL-22-treated keratinocytes (HaCaT). Knockdown of circ_0082476 reduced cell proliferation, invasion and migration in IL-22-treated HaCaT cells. Circ_0082476 induced sponge effect on miR-138-5p. Circ_0082476 regulated IL-22-induced cell injury through targeting miR-138-5p. BRD4 was confirmed as a target of miR-138-5p, and miR-138-5p relieved IL-22-induced cell dysfunction by the direct downregulation of BRD4. BRD4 was positively regulated by circ_0082476 via sponging miR-138-5p.

Conclusion: These findings disclosed that circ_0082476 facilitated the IL22-induced epidermis cell injury in psoriasis through the upregulation of BRD4 via binding to miR-138-5p.