HPV16型E6癌基因对结肠癌细胞PD-1/PD-L1表达的影响及其机制研究  

Effect of HPV16 E6 Oncogene on PD-1/PD-L1 Expression in Colon Cancer Cells and Its Mechanism

作　　者：邓晓 邱莎莎 缪作华 李伟松 DENG Xiao;QIU Shasha;MIAO Zuohua(The First Clinical Medical College,Gannan Medical University,Ganzhou City,Jiangxi Province 341000;不详)

机构地区：[1]赣南医科大学第一临床医学院,江西省赣州市341000 [2]赣南医科大学第一附属医院病理科 [3]赣南医科大学基础医学院

出　　处：《医学理论与实践》2025年第6期913-917,926,共6页The Journal of Medical Theory and Practice

基　　金：江西省教育厅科技研究立项项目(GJJ201513)。

摘　　要：目的:探讨人乳头瘤病毒(HPV)16型E6癌基因的表达与结肠癌细胞程序性死亡受体1(PD-1)及程序性死亡配体1(PD-L1)表达之间的关系。方法:运用含HPV16 E6癌基因的质粒转染HT-29和SW480结肠癌细胞株,检测PD-1、PD-L1的表达状态,同时评估对磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/AKT)、信号传导和转录激活因子3(STAT3)信号通路的影响,并通过高通量测序检测差异表达基因。结果:转染HPV16 E6癌基因后,HT-29和SW480均显示PD-1、PD-L1表达显著降低。在SW480细胞中,PI3K/AKT和STAT3蛋白的表达显著降低,但在HT-29细胞中表达显著上调,并且AKT的磷酸化水平升高。mRNA高通量测序结果显示,HPV16 E6过表达后有12843个共同表达基因,HT-29细胞中有2167个差异表达基因,SW480细胞中有2933个差异表达基因。结论:HPV16 E6可显著降低PD-1、PD-L1的表达水平,但对不同细胞中PI3K/AKT和STAT3信号通路的影响并不一致,可能存在其他调控通路途径。Objective:To explore the relationship between the expression of the human papilloma virus(HPV)type 16 E6 oncogene,programmed death receptor 1(PD-1)and programmed death ligand 1(PD-L1)in colon cancer cells.Methods:HT-29 and SW480 colon cancer cell lines were transfected with plasmids containing HPV16 E6 oncogene to detect the expression status of PD-1 and PD-L1,and to evaluate the effects on phosphatidylinositol-3-kinase/protein kinase B(PI3K/AKT),signal transducer and activator of transcription 3(STAT3)signaling pathways.Differentially expressed genes were detected by high-throughput sequencing.Results:After transfection of HPV16 E6 oncogene,the expression of PD-1 and PD-L1 was significantly decreased in both HT-29 and SW480.The expression of PI3K/AKT and STAT3 proteins was significantly reduced in SW480 cells,but significantly upregulated in HT-29 cells,and AKT phosphorylation levels were elevated.High-throughput mRNA sequencing results showed that 12843 co-expressed genes were found after overexpression of HPV16 E6,2167 differentially expressed genes were found in HT-29 cells,and 2933 differentially expressed genes were found in SW480 cells.Conclusion:HPV16 E6 can significantly reduce the expression levels of PD-1 and PD-L1,but the effects on PI3K/AKT and STAT3 signaling pathways in different cells are inconsistent,and other regulatory pathways may exist.

关 键 词：人乳头瘤病毒 结直肠癌 程序性死亡受体1 程序性死亡配体1 磷脂酰肌醇-3-激酶 

分 类 号：R73-7[医药卫生—肿瘤]