LncRNAAGAP2-AS1 Regulates MiR-424-5p/AKT3 Axis In Study On The Pathogenesis Of Psoriasis

Background:Psoriasis is a chronic,recurrent and inflammatory skin disease which is characterized by immune cell infiltration and keratinocyte hyperproliferation.However,the precise molecular mechanisms remain largely elusive.Long noncoding RNAs(lncRNAs)are longer than 200nt and have limited or no protein-coding capacity.In recent years,several lncRNAs have been reported to promote keratinocyte proliferation and established as critical regulators in the pathogenesis of psoriasis.AGAP2 antisense RNA1(AGAP2-AS1)is a newly discovered lncRNA molecule in recent years.Subsequent studies demonstrated that AGAP2-AS1 can promote cell proliferation in various cell types of cancers.However,the involvement of AGAP2-AS1 in psoriasis has not yet been reported.This study aimed to unravel the functions of lncRNA AGAP2-AS1 and its biological mechanism in psoriasis pathogenesis,hinting for the new therapeutic targets in psoriasis.Methods:1.We firstly analyzed the expression level of AGAP2-AS1 in GEO database that includes gene expression data of skin from psoriatic patients and normal healthy controls and validated the result in 14 psoriatic skin samples and 12 normal healthy controls’ skin sample by qRT-PCR.2.In keratinocyte with AGAP2-AS1 knockdown or overexpression,CCK8 and clone formation assays were utilized to assess proliferation.3.The relationships among AGAP2-AS 1,miR-424-5p and AKT3 were examined by dual-luciferase reporter assay and RNA immunoprecipitation(RIP)assay.To assess whether AGAP2-AS1 played a role in psoriasis pathogenesis via sponging miR-424-5p and regulating AKT3.Results:1.AGAP2-AS1 level was upregulated in the involved skin tissue of psoriasis patients than that of healthy controls.2.AGAP2-AS1 could promote proliferation and colony formation ability of keratinocytes.3.AGAP2-AS1 functioned as a competitive endogenous RNA by sponging miR-424-5p to upregulate AKT3 and promote cell proliferation in keratinocytes.Conclusion:AGAP2-AS1 is upregulated in the involved skin tissue of psoriasis patients.AGAP2-AS1 promotes keratinocyte proliferation through miR-424-5p/AKT3 axis and may play a role in psoriasis pathogenesis.