RESUMO
Psoriasis is a chronic inflammatory disease characterized by increased keratinocyte proliferation and local inflammation. Long noncoding RNAs (lncRNAs) play important regulatory roles in many immune-mediated diseases, including psoriasis. In this study, we aimed to investigate the role and mechanism of lnc-SPRR2G-2 (SPRR2G) in M5-treated psoriatic keratinocytes. Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction (qRT-PCR) showed that lnc-SPRR2G-2 was significantly upregulated in psoriasis tissues and psoriatic keratinocytes. In psoriatic keratinocytes, functional and molecular experiment analyses demonstrated that SPRR2G regulated proliferation, cell cycle and apoptosis, and induced the expression of S100 calcium binding protein A7 (S100A7), interleukin (IL)-1ß, IL-8 and C-X-C motif chemokine ligand 10 (CXCL10). The function of SPRR2G in psoriasis is related to the STAT3 signaling pathway and can be inhibited by a STAT3 inhibitor. Moreover, KH-type splicing regulatory protein (KHSRP) was proved to be regulated by lnc-SPRR2G-2 and to control the mRNA decay of psoriasis-related cytokines (p < 0.05). In summary, we reported the functions of lnc-SPRR2G-2 and KHSRP in psoriasis. Our findings provide new insights for the further exploration of the pathogenesis and treatment of psoriasis.
Assuntos
Proliferação de Células , Inflamação , Queratinócitos , Psoríase , RNA Longo não Codificante , Fator de Transcrição STAT3 , Transdução de Sinais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Psoríase/genética , Psoríase/patologia , Psoríase/metabolismo , Queratinócitos/metabolismo , Queratinócitos/patologia , Proliferação de Células/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Regulação para Baixo/genética , Proteína A7 Ligante de Cálcio S100/genética , Proteína A7 Ligante de Cálcio S100/metabolismo , Apoptose/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Masculino , Feminino , AdultoRESUMO
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-1ß (IL-1ß), 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.
