RNA-seq reveal RNA binding protein GNL3 as a key mediator in the development of psoriasis vulgaris by regulating the IL23/IL17 axis.

Abstract Background Psoriasis is a systemic chronic inflammatory skin disorder that was prone to recurrence. The RNA binding protein GNL3 has an important function in maintaining the proliferative ability of stem cells, and its overexpression leads to apoptosis. GNL3 is expressed in the epidermis, however, its regulatory mechanism in psoriasis vulgaris is still poorly understood. Objective To identify the role of GNL3 in the pathogenesis of psoriasis vulgaris. Materials and methods RNA-seq was performed to obtain the data of genes' expression and splicing events in Hela cells after shGNL3 and shCtrl was transferred. High quality results of differentially expressed genes (DEGs) and alternative splicing events (ASEs) were further attained by quality control and analysis. Through the functional enrichment analysis of DEGs and ASEs, the regulating effect of GNL3 was discussed, and the hypothesis was further confirmed in HaCat cells and psoriasis lesions. Results The mRNA expression of IL23A in Hela cells was upregulated in GNL3 knockdown, and the ratio of ASE occurred in TNFAIP3 was increased. However, in HaCaT cells, the mRNA expression level of IL23A was downregulated in GNL3 knockdown, and the ratio of ASE of TNFAIP3 was decreased. Additionally, the results obtained in HaCaT cells was further validated in the lesional psoriatic skin. Conclusion GNL3 takes an important part in the development of psoriasis vulgaris by regulating the IL23/IL17 axis, which may serve as the basis of effective targeted treatment in future.