CircVAPA contributes to hyper-proliferation and inflammation of keratinocytes through miR-125b-5p/sirt6 axis in psoriasis

Psoriasis is an autoimmune skin disease with abnormal keratinocyte hyperproliferation. The important roles of circular RNAs (circRNAs) in various inflammatory diseases have been revealed. The present study aimed to investigate the roles of circVAPA and its molecular mechanisms in psoriasis. Quantitative real-time polymerase chain reaction was performed to measure the RNA expression. Enzyme-linked immunosorbent assays were employed to examine the production of inflammatory factors. Cell-counting kit-8, EDU and flow cytometry assay were conducted to examine the cell viability, proliferation and apoptosis respectively. Dual-luciferase reporter assay and ribonucleoprotein immunoprecipitation (RIP) were conducted to verify the target relationship between miR-125b-5p and circVAPA or Sirt6. Herein our findings showed increased expression of circVAPA and Sirt6 and decreased level of miR-125b-5p in psoriatic lesional tissues and M5-stimulated keratinocytes. Mechanistically, circVAPA knockdown significantly suppressed the promotion of M5 on cell viability, proliferation, and inflammation of HaCaT cells. circVAPA was verified to interact with miR-125b-5p, while inhibition of miR-125b-5p counteracted circVAPA knockdown-mediated effects in M5-stimulated HaCaT cells. Sirt6 was confirmed as a target of miR-125b-5p, and miR-125b-5p overexpression inhibited cell growth and inflammation partly by targeting Sirt6 in M5-stimulated HaCaT cells. Moreover, circVAPA was featured as a competing endogenous RNA by directly sponging miR-125b-5p to up-regulate the expression of Sirt6. CircVAPA participate in the progression of psoriasis through miR-125b-5p/sirt6 axis by regulating proliferation and inflammation of keratinocytes, highlighting a potential therapeutic target for psoriasis.