miRNA-200b通过调控PD-L1/PD-1信号通路在结肠癌中的作用  

Effect of MiRNA-200b in Colon Cancer by Regulating PD-L1/PD-1 Signaling Pathway

作　　者：张骞 刘海东[1] 乌日嘎 张宸荣 王宇光[1] ZHANG Qian;LIU Hai-dong;WU Ri-ga;ZHANG Chen-rong;WANG Yu-guang(Department of Coloproctology,Second Affiliated Hospital of Baotou Medical College,Inner Mongolia University of Science and Technology,Baotou,Inner Mongolia 014030)

机构地区：[1]内蒙古科技大学包头医学院第二附属医院肛肠科,内蒙古包头014030

出　　处：《中国肛肠病杂志》2024年第10期1-5,共5页Chinese Journal of Coloproctology

基　　金：包头医学院中青年科技骨干支持计划项目(编号H16)。

摘　　要：目的:探讨miRNA-200b在结直肠癌肿瘤生长和免疫逃逸中的作用,以及其与PD-1/PD-L1通路之间的分子联系。方法:构建miRNA-200b过表达和抑制表达慢病毒载体。建立BALB/c小鼠CT-26细胞皮下移植瘤模型。将小鼠随机分为对照组、miRNA-200b过表达组和miRNA-200b抑制组,每组10只。测量肿瘤体积和质量,进行HE染色观察病理学变化。采用实时荧光定量PCR检测miRNA-200b、PD-1和PD-L1的mRNA表达水平。结果:miRNA-200b过表达组肿瘤体积和质量显著小于对照组,抑制组则显著大于对照组。HE染色显示miRNA-200b过表达组肿瘤细胞增殖活性降低,出现退行性变化。miRNA-200b过表达组中miRNA-200b表达上调,PD-1和PD-L1表达下调;抑制组则相反。miRNA-200b表达水平与PD-1和PD-L1 mRNA表达水平呈负相关。结论:miRNA-200b可能通过抑制PD-1/PD-L1通路来抑制结直肠癌的肿瘤生长和免疫逃逸,为结直肠癌免疫治疗提供了新的潜在靶点。Objective To investigate the effect of miRNA-200b in tumor growth and immune escape of colorectal cancer and molecular association with the PD-1/PD-L1 pathway.Methods The lentiviral vec-tors of miRNA-200b over-expression and inhibitory expression were constructed.The subcutaneous trans-plantation tumor model of CT-26 cells in BALB/c mice was established.The mice were randomly divided into control group,miRNA-200b over-expression group and miRNA-200b inhibition group,with 10 mice in each group.The volume and mass of the tumor were measured and the pathological changes were observed by HE staining.The mRNA expression levels of miRNA-200b,PD-1 and PD-L1 were detected by real-time PCR.Results The tumor volume and mass in the miRNA-200b over-expression group were significantly smaller than those in the control group,while those in the inhibition group were significantly larger than those in the control group.HE staining showed that the proliferation activity of tumor cells in the miRNA-200b over-expression group decreased,appearing degenerative changes.In the miRNA-200b over-expres-sion group,the expression of miRNA-200b was up-regulated,and the expression of PD-1 and PD-L1 was down-regulated,which was opposite in the inhibition group.The expression level of miRNA-200b was neg-atively correlated with the mRNA expression levels of PD-1 and PD-L1.Conclusion MiRNA-200b may inhibit tumor growth and immune escape of colorectal cancer by inhibiting PD-1/PD-L1 pathway,providing a new potential target for colorectal cancer immunotherapy.

关 键 词：结直肠癌 肿瘤免疫逃逸 PD-1/PD-L1 MicroRNA-200b 免疫治疗 

分 类 号：R735.35[医药卫生—肿瘤]