小鼠舌白斑的转录组学特征和信号通路改变及白介素17A单抗治疗的实验研究OACSTPCD

Objective:To explore the transcriptomic characteristics and signal pathway changes of mouse tongue leu-koplakia formation and malignant progression,as well as the therapeutic effect of interleukin-17A(IL-17A)monoclonal anti-body on mouse tongue leukoplakia.Methods:RNA-sequence was performed on human normal tongue mucosa tissues(NM),tongue leukoplakia(OL)tissues with epithelial dysplasia from the same patient,normal mucosa tissues,and leukoplakia tis-sues(mOL)from the tongue of 4NQO-induced mice.After 12 weeks of 4NQO induction,the mice were divided into two groups:experimental group(intraperitoneal injection of anti-mouse IL-17A monoclonal antibody)and control group(intraper-itoneal injection of IgG1 isotype control antibody),the dosage of monoclonal antibody was 10 mg/kg/w.Tissue samples were collected after four weeks'injection.And the histopathology of the mouse tongues were performed by hematoxylin-eosin stai-ning(HE staining)and immunohistochemistry staining(IHC)of Ki67.In vitro,the leukoplakia cell lines(DOK,Leuk1)were stimulated with recombinant human IL-17A respectively and cell cycle was analyzed by flow cytometry.Results:Comprehen-sive analysis of the transcriptomic sequencing results of humans and mice showed that the IL-17 signaling pathway was signif-icantly upregulated during leukoplakia formation.The histopathological evaluation results after four weeks of Anti-mouse IL-17A monoclonal antibody treatment showed that 80％of the mouse tongues in the experimental group had mild to moderate epithelial dysplasia,while 20％had severe epithelial dysplasia.In the control group,40％had mild to moderate epithelial dys-plasia,40％had severe epithelial dysplasia,but 20％had infiltrating cancer.The results of Ki67 showed that the proportion of cells in the proliferation stage in the control group was significantly higher than that in the control group(P＜0.05).And flow cytometry showed that IL-17A stimulation led to more concentration of cells in the S-G2-M phase(P＜0.05).Conclusion:The IL-17 signaling pathway is significantly upregulated during the formation and malignant progression of leukoplakia in hu-man and mice tongues.Anti-mouse IL-17A monoclonal antibody has potential therapeutic effect on 4NQO-induced mouse tongue leukoplakia.IL-17A promotes the proliferation of leukoplakia cells.