IL-22/IL-22RA1通路在口腔鳞状细胞癌恶性进展中的作用及其机制  

Role of IL-22/IL-22RA1 pathway in the malignant progression of oral squamous carcinoma and its mechanism

作　　者：张晗 甘桂芳 ZHANG Han;GAN Guifang(Department of Clinical Laboratory,Shanghai Ninth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200011,China)

机构地区：[1]上海交通大学医学院附属第九人民医院检验科,上海200011

出　　处：《中国肿瘤生物治疗杂志》2024年第1期19-26,共8页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金青年项目(No.82203551);上海市“医苑新星”青年医学人才培养资助计划(No.沪卫人事[2020]087号);上海交通大学医工交叉项目(No.YG2022QN065)。

摘　　要：目的:探讨IL-22/IL-22受体A1(IL-22RA1)通路在口腔鳞状细胞癌(OSCC)恶性进展中的作用及其机制。方法:利用GEO数据库和免疫组化法分析IL-22RA1在OSCC组织及配对癌旁组织中的表达水平,采用组织芯片免疫组化法检测并分析IL-22RA1表达水平与OSCC患者临床病理特征的关系,通过EBI ArrayExpress数据库分析IL-22RA1表达水平与患者预后的关系。采用免疫荧光法检测IL-22和IL-22RA1在OSCC组织中表达水平并分析两者间的相关性。用RNA干扰技术敲减OSCC细胞WSU-HN4和CAL27的IL-22RA1表达,用q PCR法验证敲减效率。采用克隆形成实验、Transwell小室法分别检测IL-22对阴性对照(si NC)组和IL-22RA1敲减(siIL-22RA1)组OSCC细胞克隆形成及迁移能力的影响,WB法检测IL-22对OSCC细胞IL-22RA1表达水平及STAT1、STAT3和ERK1/2磷酸化水平的影响。结果:OSCC组织中IL-22RA1 mRNA的表达水平显著高于癌旁组织(P<0.05)。IL-22RA1表达水平与OSCC患者的肿瘤大小(P<0.05)、淋巴结转移(P<0.01)及预后不良(P<0.05)有关联。OSCC组织中的IL-22和IL-22RA1表达水平无明显关联,IL-22对OSCC细胞IL-22RA1表达无影响(均P>0.05)。IL-22可显著增强OSCC细胞的克隆形成和迁移能力(均P<0.01),并可激活OSCC细胞的STAT1、STAT3及ERK1/2信号分子;敲减OSCC细胞的IL-22RA1后,IL-22则无法发挥上述作用。结论:IL-22/IL-22RA1可通过调控细胞增殖和迁移促进OSCC的生长和转移,其下游机制可能是激活ERK1/2-STAT1/3信号通路。Objective:To investigate the role of IL-22/IL-22RA1(IL-22 receptor A1) pathway in the malignant progression of oral squamous cell carcinoma(OSCC) and the underlying mechanisms.Methods:The expression levels of IL-22RA1 in OSCC tissues and paired paracancerous tissues were analyzed using the GEO database and immunohistochemistry.The association between IL-22RA1 expression and the clinicopathological characteristics of OSCC patients was detected and analyzed by tissue microarray immunohistochemistry.The relationship between IL-22RA1 expression and the prognosis of OSCC patients was analyzed using the EBI ArrayExpress database.The expression of IL-22 and IL-22RA1 in OSCC tissues was examined by immunofluorescence,and their association was also analyzed.IL-22RA1expression was knocked down in OSCC WSU-HN4 and CAL27 cells by RNA interference technology,and the efficiency was verified using qPCR.The effects of IL-22 on the colonogenesis and migration of OSCC cells in the negative control(siNC) group and IL-22RA1knock-down(siIL-22RA1) group were determined by plate cloning and transwell assays,respectively.The effects of IL-22 on the expression of IL-22RA1 and the phosphorylation level of STAT1,STAT3 and ERK1/2 in OSCC cells were detected using the WB assay.Results:The m RNA expression of IL-22RA1 in OSCC tissues was significantly higher than that in para-cancerous tissues(P<0.05).The expression of IL-22RA1 was associated with tumor size(P<0.05),lymph node metastasis(P<0.01),and poor prognosis(P<0.05) of OSCC patients.There was no significant correlation between the expression levels of IL-22 and IL-22RA1 in OSCC tissues,and IL-22 did not affect on the expression level of IL-22RA1 in OSCC cells(all P>0.05).IL-22 significantly enhanced the colony formation and migration abilities(all P<0.01) of OSCC cells,and activated STAT1,STAT3 and ERK1/2 signals in OSCC cells.After knocking down IL-22RA1 in OSCC cells,IL-22 could not exert the above effects.Conclusion:IL-22/IL-22RA1 can promote the growth and metastasis of OSCC by regu

关 键 词：IL-22 IL-22受体A1 口腔鳞状细胞癌 WSU-HN4细胞 CAL27细胞 增殖 迁移 

分 类 号：R739.8[医药卫生—肿瘤] R730.2[医药卫生—临床医学]