Kruppel样因子14介导的JAK-STAT信号通路对非小细胞肺癌预后的影响  

Effect of the KLF14⁃mediated JAK⁃STAT signaling pathway on prognosis of lung cancer

作　　者：王鹏 姚苏梅[1] 吕学东[1] 陈金亮[1] WANG Peng;YAO Sumei;LV Xuedong;CHEN Jinliang(Department of Respiratory,Nantong First People's Hospital,Nantong 226000,China)

机构地区：[1]南通市第一人民医院呼吸科,江苏南通226000

出　　处：《实用医学杂志》2024年第1期25-31,共7页The Journal of Practical Medicine

基　　金：江苏省卫生健康委员会科研项目(编号:M20200096);南通市科技计划项目(编号:JCZ18130)。

摘　　要：目的探讨Kruppel样因子14(KLF14)介导的Janus激酶-信号转导子与转录激活子(JAKSTAT)信号通路对非小细胞肺癌(NSCLC)预后的影响。方法收集2018年1月至2019年9月本院手术切除的80例NSCLC组织和25例癌旁非肿瘤组织。患者随访至2023年4月结束。采用免疫组织化学检测组织中KLF14表达,根据KLF14表达的中值水平将患者分为高表达组和低表达组。通过在A549细胞中转染KLF14、JAK1过表达质粒和在HCC827细胞中转染KLF14、JAK1特异性短发夹RNA(shKLF14、shJAK1)来过表达或敲低KLF14、JAK1。采用细胞克隆形成试验分析细胞的增殖活力。Transwell分析细胞的迁移、侵袭情况。结果与癌旁正常组织相比,KLF14在NSCLC组织中表达降低(P<0.001)。KLF14的低表达与肿瘤直径>3 cm、淋巴结转移、临床分期Ⅲ期显著相关(P<0.05)。在高KLF14表达组和低KLF14表达组之间的总存活率有显著差异,低KLF14表达的患者预后不良(P<0.05)。KLF14过表达后,A549细胞的增殖能力、迁移和侵袭细胞数均显著降低(P<0.05),而KLF14敲低后,HCC827细胞的增殖能力、迁移和侵袭细胞数均显著增加(P<0.05)。与Vector+KLF14组相比,JAK1+KLF14组A549细胞的集落数、迁移和侵袭数显著增加(P<0.05);而与shNC+shKLF14组相比,shJAK1+shKLF14组HCC827细胞的集落数、迁移和侵袭数显著降低(P<0.05)。结论KLF14低表达与NSCLC患者较差的总生存期相关。KLF14上调显著抑制肺癌细胞在体外的增殖、转移能力,其作用机制可能与抑制JAK-STAT信号通路有关。Objective To investigate the influence of the Janus kinase‐signal transducer and transcription activator(JAK‐STAT)signaling pathway mediated by Kruppel‐like factor 14(KLF14)on the prognosis of non‐small cell lung cancer(NSCLC).Methods From January 2018 to September 2019,NSCLC tissues from 80 patients and malignancy‐free paracancerous tissues from 25 patients were collected.Medical follow‐up ended in April 2023.Immunohistochemistry was used to detect the expression of KLF14 in tissues,and the patients were divided into a high‐expression group and a low‐expression group according to the median level of KLF14 expression.Over‐expres‐sion or knock‐down of KLF14 and JAK1 was achieved by transfection of KLF14 and JAK1 overexpression plasmid in A549 cells and transfection of KLF14 and JAK1 specific short hairpin RNA(shKLF14 and shJAK1)in HCC827 cells.The proliferation activity of cells was analyzed by cell clone formation test.Transwell analyzed the migration and invasion of cells.Results As compared with the normal paracancerous tissues,the expression of KLF14 in NSCLC tissue decreased(P<0.001).The low expression of KLF14 was significantly correlated with tumor diameter of>3 cm,lymph node metastasis and clinical stageⅢ(P<0.05).There was a significant difference in the overall survival rate between the high KLF14 expression group and the low KLF14 expression group,and the patients with low KLF14 expression had poor prognosis(P=0.039).After overexpression of KLF14,the proliferation ability of A549 cells and the number of migration and invasion of these cells decreased significantly(P<0.05);while after knock‐down of KLF14,the proliferation ability of HCC827 cells and the number of migration,and invasion of these cells increased significantly(P<0.05).As compared with Vector+KLF14 group,the number of colonies,migration and invasion of A549 cells in JAK1+KLF14 group increased significantly(P<0.05).As compared with shNC+shKLF14 group,the number of colonies,migration and invasion of HCC827 cells in shJ

关 键 词：Kruppel样因子14 Janus激酶-信号转导子与转录激活子 非小细胞肺癌 预后 

分 类 号：R734.2[医药卫生—肿瘤]