Long Non-Coding RNA-GDA-1 Promotes Keratinocyte Proliferation and Psoriasis Inflammation by Regulating the STAT3/NF-κB Signaling Pathwayvia Forkhead Box M1.

Abstract

Psoriasis is a chronic inflammatory skin disease associated with multiple comorbidities and complex pathogenesis. Long non-coding RNAs (lncRNAs) play an important regulatory role in many diseases, including psoriasis. In this study, We aimed to investigate the role and mechanism of lncRNA GDA-1 (GDA) in M5-treated psoriatic keratinocytes. GDA expression was significantly upregulated in psoriatic tissues and M5-treated keratinocytes. By silencing and overexpressing GDA in NHEKs and Ker-CT cells, we showed that GDA regulated proliferation and cell cycle and increased secretion of interleukin-1β (IL-1β), IL-6, and chemokine ligands 2 and 20 (CCL2 and CCL20). RNA sequencing after GDA silencing led to the identification of a close regulatory relationship between GDA and Forkhead Box M1 (FOXM1). GDA significantly influenced FOXM1 expression at both mRNA and protein levels and activated STAT3/NF-κB signaling pathways. STAT3 and NF-κB inhibition abrogated GDA effects on keratinocyte proliferation and inflammation. In conclusion, our study is the first to report that Lnc-GDA-1 distinctly regulates FOXM1 expression and mediates proliferation and inflammation of psoriatic keratinocytes through the STAT3/NF-κB signaling pathway, which may be a potent target for psoriasis treatment.