KHSRP高表达促进胃腺癌转移:JAK1/STAT3信号轴的介导作用  

High KHSRP expression promotes gastric adenocarcinoma metastasis:the mediating role of the JAK1/STAT3 signaling axis

作　　者：张卉[1] 刘洋洋 李霞鹏 王梦瑶 李丽 韦海涛 ZHANG Hui;LIU Yangyang;LI Xiapeng;WANG Mengyao;LI Li;WEI Haitao(Department of Gastroenterology,Huaihe Hospital,Henan University,Kaifeng 475001,China;Institute of Nursing and Health,Henan University,Kaifeng 475001,China;Department of Thoracic Surgery,Huaihe Hospital,Henan University,Kaifeng 475001,China)

机构地区：[1]河南大学淮河医院消化科,河南开封475001 [2]河南大学护理与健康学院慢病研究所,河南开封475004 [3]河南大学淮河医院胸外科,河南开封475001

出　　处：《南方医科大学学报》2024年第9期1760-1768,共9页Journal of Southern Medical University

基　　金：河南省教育厅资助项目(24A320002);河南省科技厅指导项目(242102310100,242102310184)河南省科技厅指导项目(242102310197,242102310280)。

摘　　要：目的探究KHSRP通过JAK1/STAT3信号轴调控胃腺癌转移恶性进展及其潜在的分子机制。方法采用qRT-PCR检测胃腺癌细胞系(MKN-28、HGC-27、CRL-5822、SNU-1)及人正常胃黏膜细胞系(GES-1)中KHSRP的表达量。CCK-8、Transwell迁移/侵袭实验分别检测细胞增殖、迁移和侵袭等生物学特征。采用Western blotting法检测稳定转染细胞中JAK/STAT、KHSRP蛋白的表达水平。将HGC-27、SNU-1注射至裸鼠体内,对裸鼠进行皮下荷瘤敲降组(5只/组)和过表达组(5只/组)和尾静脉注射模型实验敲降组(5只/组)和过表达组(5只/组),观察STAD细胞在裸鼠体内的生长情况。结果qRT-PCR结果显示,与人正常胃腺癌黏膜上皮细胞(GES-1)和组织相比,KHSRP在胃腺癌细胞系(MKN-28、HGC-27、CRL-5822、SNU-1)和肿瘤组织中的表达显著升高(P<0.05)。细胞功能实验显示,与sh-NC组相比,sh-KHSRP组HGC-27细胞抑制细胞增殖、细胞迁移、侵袭,Vector组SNU-1细胞促进细胞增殖、迁移、侵袭(P<0.05)。裸鼠实验中,与sh-NC组相比,sh-KHSRP组裸鼠肿瘤体积和质量、细胞增殖率和胃腺癌转移病灶数目明显减少(P<0.05);过表达结果相反(P<0.05)。信号通路实验显示,与sh-NC组相比,sh-KHSRP组JAK1、STAT3的表达量显著下调(P<0.05),过表达组结果相反(P<0.05)。结论KHSRP可通过JAK1/STAT3信号轴,促进胃腺癌转移的恶性进程。Objective To investigate the regulatory effect of KHSRP on progression of gastric adenocarcinoma and the role of the JAK1/STAT3 signaling axis in mediating its effect.Methods KHSRP mRNA expression level was detected using qRT-PCR in 120 pairs of gastric adenocarcinoma and adjacent tissues,4 gastric adenocarcinoma cell lines(MKN-28,HGC-27,CRL-5822,and SNU-1)and normal human gastric mucosal GES-1 cells.In HGC-27 cells with KHSRP knockdown and SNU-1 cells with KHSRP overexpression,cell proliferation,migration,invasion and expression levels of JAK/STAT were evaluated using CCK-8 assay,Transwell migration and invasion assays,and Western blotting.In BALB/c-nude mice,HGC-27 cells with KHSRP knockdown and SNU-1 cells overexpressing KHSRP were injected either subcutaneous or via the tail vein to observe subcutaneous xenograft growth and lung metastasis of the tumor cells.Results Gastric adenocarcinoma tissues and cell lines all showed significantly increased KHSRP expression as compared with the adjacent tissues and GES-1 cells.In HGC-27 cells,KHSRP knockdown significantly inhibited cell proliferation,migration and invasion,while KHSRP overexpression enhanced the malignant behaviors of SNU-1 cells.In nude mice,inoculation of HGC-27 cells with KHSRP knockdown resulted in smaller tumor volume and weight,slower cell proliferation rate and fewer lung metastatic foci,and KHSRP-overexpressing SNU-1 cells produced the opposite results.KHSRP knockdown in HGC-27 cells significantly down-regulated the expression levels of JAK1 and STAT3,which were obviously increased in KHSRP-overexpressing SNU-1 cells.Conclusion High expressions of KHSRP promote progression and metastasis of gastric adenocarcinoma possibly by regulating the JAK1/STAT3 signaling axis.

关 键 词：胃腺癌 分子机制 JAK1 STAT3 KHSRP 

分 类 号：R735.2[医药卫生—肿瘤]