基于JAK/STAT信号通路探讨PRELID1表达在胃癌恶性生物学行为中的作用  

Effects of PRELID1 expression on malignant biological behaviors of gastric cancer based on JAK/STAT signaling pathway

作　　者：夏勇生 赵萌 杨一群 马珍丽 桑梦倩 陈德利[1] XIA Yongsheng;ZHAO Meng;YANG Yiqun;MA Zhenli;SANG Mengqian;CHEN Deli(Department of Gastrointestinal Surgery,First Affiliated Hospital of Bengbu Medical College,Bengbu 233004,China;Bengbu Medical College,Bengbu 233030,China;Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-related Diseases,Bengbu Medical College,Bengbu 233004,China;Anhui Provincial Key Laboratory of Tissue Transplantation,Bengbu Medical College,Bengbu 233030,China)

机构地区：[1]蚌埠医学院第一附属医院胃肠外科,蚌埠233004 [2]蚌埠医学院,蚌埠233030 [3]蚌埠医学院炎症相关性疾病基础与转化研究安徽省重点实验室,蚌埠233004 [4]蚌埠医学院组织移植安徽省重点实验室,蚌埠233030

出　　处：《临床与实验病理学杂志》2024年第2期164-171,共8页Chinese Journal of Clinical and Experimental Pathology

基　　金：安徽省高校自然科学基金重点项目(KJ2021A0685);研究生科研创新计划项目(Byycxz23045)。

摘　　要：目的探讨相关进化和淋巴兴趣域蛋白1(PRELID1)在胃癌组织中的表达及对预后的影响,并分析其影响胃癌细胞增殖和侵袭能力的机制。方法利用TCGA数据库和111例胃癌患者的临床数据分析PRELID1在胃癌组织中的表达,并分析PRELID1表达与临床病理特征的关系及对预后的影响。生物信息学技术预测PRELID1的生物学功能,并进一步采用体外和体内实验验证。体外实验检测慢病毒调控胃癌细胞系(MGC803)中PRELID1的表达,并观察其对胃癌细胞增殖、迁移和侵袭的影响。利用裸鼠皮下成瘤体内实验观察PRELID1表达对胃癌组织生长的影响。结果PRELID1在胃癌组织中的表达显著高于癌旁组织(P<0.001)且与Ki67增殖指数呈正相关(P<0.001)。Cox回归模型分析显示,PRELID1高表达是影响胃癌患者根治术后5年生存率的独立危险因素(HR=2.336;95%CI=1.354~4.029)。基因富集结果显示,PRELID1的功能与细胞增殖和JAK/STAT信号有关。CCK-8和Transwell实验发现上调PRELID1表达可促进胃癌细胞的增殖(P=0.016)、迁移(P=0.016)和侵袭(P=0.025),下调其表达则抑制胃癌细胞的增殖(P=0.026)、迁移(P=0.048)和侵袭(P=0.029);裸鼠皮下成瘤实验发现上调PRELID1表达可促进胃癌组织的生长(P=0.047),下调其表达结果相反(P=0.005)。Western blot法检测结果显示,上调PRELID1表达可促进胃癌细胞和胃癌组织中JAK和STAT蛋白的表达(P均<0.05),下调则抑制(P均<0.05)。结论PRELID1在胃癌组织中呈高表达且与预后不良相关,其可能通过上调JAK/STAT信号调控胃癌细胞的增殖、迁移和侵袭。Purpose To investigate the expression of protein of relevant evolutionary and lymphoid interest domain-containing 1(PRELID1)in gastric cancer tissues and to analyze its effect on prognosis,and the mechanism of influencing the proliferation and invasion ability of gastric cancer cells.Methods Using TCGA data and clinical data of 111 patients with gastric cancer,we analyzed the relationship between the expression of PRELID1 and clinicopathological parameters and the impact on clinical prognosis.The biological function of PRELID1 was predicted by bioinformatics,and further verified by in vitro and in vivo experiments.Lentivirus was applied to regulate the level of PRELID1 in gastric cancer cell line(MGC803)in vitro,and its effect on the proliferation,migration,and invasion of gastric cancer cells was observed.The nude mouse subcutaneous tumorigenesis was used to observe the effect of PRELID1 on the growth of gastric cancer tissue in vivo.Results The expression of PRELID1 was significantly higher in gastric cancer tissues than that in the adjacent tissues(P<0.001)and was positively correlated with the cell proliferation indicator Ki67(P<0.001).Cox regression model analysis showed that the high expression of PRELID1 was an independent risk factor affecting the 5-year survival rate after radical gastrectomy(HR=2.336;95%CI=1.354-4.029).Gene enrichment results showed that the function of PRELID1 was related to proliferation and JAK/STAT signaling.CCK-8 and Transwell experiments found that up-regulation of PRELID1 promoted the proliferation(P=0.016),migration(P=0.016)and invasion(P=0.025)of gastric cancer cells,while down-regulation inhibited the proliferation(P=0.026),migration(P=0.048)and invasion(P=0.029).Subcutaneous tumor formation experiments in nude mice found that up-regulation of PRELID1 promoted the growth of gastric cancer tissue(P=0.047),while down-regulation was the opposite(P=0.005).Western blot detecting gastric cancer cells and gastric cancer tissues found that up-regulation of PRELID1 promoted the express

关 键 词：胃肿瘤 相关进化和淋巴兴趣域蛋白1 增殖 侵袭 JAK/STAT信号 

分 类 号：R735.2[医药卫生—肿瘤]