首页|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

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

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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 pro-tein of relevant evolutionary and lymphoid interest domain-con-taining 1(PRELID1)in gastric cancer tissues and to analyze its effect on prognosis,and the mechanism of influencing the prolif-eration 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 pre-dicted by bioinformatics,and further verified by in vitro and in vivo experiments.Lentivirus was applied to regulate the level of PRELID 1 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 tumor-igenesis 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 cor-related with the cell proliferation indicator Ki67(P<0.001).Cox regression model analysis showed that the high expression of PRELID 1 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 func-tion of PRELID1 was related to proliferation and JAK/STAT sig-naling.CCK-8 and Transwell experiments found that up-regula-tion of PRELID1 promoted the proliferation(P=0.016),mi-gration(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 oppo-site(P=0.005).Western blot detecting gastric cancer cells and gastric cancer tissues found that up-regulation of PRELID1 promoted the expression of JAK and STAT proteins(all P<0.05),while down-regulation inhibited them(all P<0.05).Conclusion The high expression of PRELID1 associated with poor prognosis may regulate the proliferation,migration and in-vasion of gastric cancer cells by up-regulating JAK/STAT signa-ling in gastric cancer.

gastric neoplasmsPRELID1proliferationinva-sionJAK/STAT signaling

夏勇生、赵萌、杨一群、马珍丽、桑梦倩、陈德利

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蚌埠医学院第一附属医院胃肠外科,蚌埠 233004

蚌埠医学院,蚌埠 233030

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

蚌埠医学院组织移植安徽省重点实验室,蚌埠 233030

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胃肿瘤 相关进化和淋巴兴趣域蛋白1 增殖 侵袭 JAK/STAT信号

安徽省高校自然科学基金重点项目研究生科研创新计划项目

KJ2021A0685Byycxz23045

2024

临床与实验病理学杂志
安徽医科大学,中华医学会安徽分会

临床与实验病理学杂志

CSTPCD北大核心
影响因子:0.776
ISSN:1001-7399
年,卷(期):2024.40(2)
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