Long non-coding RNA-GDA-1 Regulates Keratinocyte Proliferation and Psoriasis Inflammation by Regulating Forkhead Box M1 via the STAT3/NF-κB Signaling Pathway

Abstract

Abstract Psoriasis is a chronic inflammatory skin disease associated with multiple comorbidities and complex pathogenesis. Long noncoding 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, chemokine ligands 2 and 20 (CCL2 and CCL20). RNA sequencing after GDA silencing led to 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.