非小细胞肺癌中HAT1过表达与PD-L1间的免疫调控关系  

Immunoregulatory relationship between HAT1 overexpression and PD-L1 in non-small cell lung cancer

作　　者：田文[1] 李永生[1] 魏志江[1] 赵金慧 王倩 TIAN Wen;LI Yongsheng;WEI Zhijiang;ZHAO Jinhui;WANG Qian(Second Department of Oncology,Cangzhou Central Hospital,Cangzhou 061000,China)

机构地区：[1]沧州市中心医院肿瘤内二科,061000

出　　处：《免疫学杂志》2021年第12期1094-1098,共5页Immunological Journal

摘　　要：目的观察组蛋白乙酰转移酶1(histone acetyltransferase 1,HAT1)对肺癌细胞程序性细胞死亡蛋白配体1(PD-L1)表达的调节作用,分析其介导肿瘤免疫的机制。方法收集2019年10月至2020年10月医院手术切除的57例非小细胞肺癌(NSCLC)组织及其癌旁组织石蜡切片,购置人胚肺成纤维细胞(HFL1)和人非小细胞肺癌细胞(A549),RT-PCR法测定经转染慢病毒载体构建的组织和细胞模型中HAT1和PD-L1 m RNA表达量。先构建HAT1过表达模型,将细胞随机分为sh-HAT1组和sh-NC组。通过转染siRNA构建HAT1低表达模型,将细胞随机分为si-HAT1组和si-NC组。分别采用MTT法和细胞划痕实验观察细胞增殖和迁移能力。结果NSCLC组织HAT1和PD-L1 mRNA相对表达量显著高于癌旁组织(P<0.05),且NSCLC组织中HAT1和PD-L1 mRNA表达呈正相关(P<0.05);A549细胞HAT1和PD-L1 m RNA相对表达量高于HFL1细胞(P<0.05);shHAT1组细胞增殖活力高于sh-NC组,si-HAT1组细胞增殖活力低于si-NC组(P<0.05);sh-HAT1组细胞划痕距离大于sh-NC组,si-HAT1组细胞划痕距离小于si-NC组(P<0.05);sh-HAT1组PD-L1 mRNA相对表达量高于sh-NC组,si-HAT1组(P<0.05);si-HAT1组PD-L1 mRNA相对表达量低于si-NC组(P<0.05)。结论HAT1与PD-L1在NSCLC组织和细胞中表达有正相关关系,HAT1可通过上调PD-L1,促进细胞增殖和迁移,从而介导肿瘤免疫逃逸。This study was performed to investigate the regulatory effect of histone acetyltransferase 1(HAT1)on the expression of programmed cell death protein ligand 1(PD-L1)in lung cancer cells,and evaluate its mechanism in mediating tumor immunity.Total of 57 cases of non-small cell lung cancer(NSCLC)tissue and paracarcinoma tissue paraffin sections were collected from patients during October 2019 to October 2020.Human embryonic lung fibroblasts HFL1 and human non-small cell lung cancer cells A549 were purchased to construct cell model.RT-PCR was used to determine the expression of HAT1 and PD-L1 mRNA in tissues and cell models constructed by transfected lentiviral vectors.First,the HAT1 overexpression model were constructed,and the cells were randomly divided into sh-HAT1 group and sh-NC group.Then the HAT1 low expression model was constructed by transfection of siRNA,and the cells were randomly divided into si-HAT1 group and si-NC group.MTT assay and scratch test were used to observe cell proliferation and migration.Data showed that the expression of HAT1 and PD-L1 mRNA in NSCLC tissue were significantly higher than those in adjacent tissues(P<0.05),and the expression of HAT1 and PD-L1 mRNA in NSCLC tissue was positively correlated(P<0.05).The expression of HAT1 and PD-L1 mRNA in A549 cells were higher than those in HFL1 cells(P<0.05);the proliferation activity of cells in the sh-HAT1 group was higher than that in the sh-NC group,and the cell proliferation activity in the siHAT1 group was lower than that in the si-NC group(P<0.05);the scratch distance of cells in the sh-HAT1 group was greater than that of the sh-NC group,and the cell scratch distance of the si-HAT1 group was shorter than that of the si-NC group(P<0.05);the expression of PD-L1 mRNA in the sh-HAT1 group was higher than that of the sh-NC group and si-HAT1 group(P<0.05);the relative expression of PD-L1 mRNA in si-HAT1 group was lower than that of si-NC group(P<0.05).In conclusion,there is a positive correlation between HAT1 and PD-L1 expression in NSCLC ti

关 键 词：非小细胞肺癌 肿瘤免疫 凋亡 

分 类 号：R73[医药卫生—肿瘤]