宫颈癌组织和细胞中PAGE4的表达及其对癌细胞增殖、凋亡和迁移的影响  

Expression of PAGE4 in cervical cancer tissues and cells and its effects on proliferation,apoptosis and migration of cancer cells

作　　者：王敏[1] 王冰琦 谭珊 刘蕾 谢可忻 李先平[1] WANG Min;WANG Bingqi;TAN Shan;LIU Lei;XIE Kexin;LI Xianping(Department of Laboratory Medicine,the Second Xiangya Hospital of Central South University,Hunan Changsha 410000,China)

机构地区：[1]中南大学湘雅二医院检验医学科,湖南长沙410000

出　　处：《现代肿瘤医学》2022年第21期3848-3856,共9页Journal of Modern Oncology

基　　金：湖南省自然科学基金(编号:2019JJ40418);中南大学研究生科研创新项目(编号:2021zzts1049)。

摘　　要：目的:探究前列腺相关基因4(prostate-related gene 4,PAGE4)在宫颈癌组织和细胞中的表达及其对癌细胞增殖、凋亡和迁移的影响。方法:根据前期组学结果,已筛选出宫颈癌中显著差异表达的基因PAGE4。IHC和RT-qPCR检测PAGE4在宫颈癌组织和细胞中的水平。构建并验证PAGE4过表达载体,随后转染宫颈癌SiHa和HeLa细胞系,运用CCK-8实验、克隆形成实验、流式细胞术、划痕愈合实验、Transwell迁移实验和Western blotting探究PAGE4对宫颈癌细胞增殖、细胞周期、凋亡、迁移和上皮间质转化的影响。应用STRING数据库预测PAGE4的潜在互作分子c-Jun,RT-qPCR检测其在过表达PAGE4的宫颈癌细胞系中的水平。通过沉默c-Jun和回复实验初步探究c-Jun在PAGE4介导的宫颈癌细胞转移中的作用。结果:测序结果表明PAGE4在宫颈癌组织中表达明显下调,倍数约为457倍。PAGE4在宫颈癌组织及细胞系中均呈低表达。与对照组相比,过表达PAGE4组细胞增殖、细胞周期以及凋亡无明显差异,但细胞迁移明显减弱,E-cadherin蛋白表达上调且Vimentin蛋白表达下调。c-Jun逆转过表达PAGE4对宫颈癌细胞迁移和上皮间质转化的影响。结论:过表达PAGE4能抑制宫颈癌细胞的迁移和上皮间质转化,其机制可能与c-Jun相关。总之,PAGE4可能在宫颈癌的转移中起一定作用,PAGE4有望成为抑制肿瘤转移的新靶点。Objective:To explore the expression of prostate-related gene 4(PAGE4)in cervical cancer tissues and cells and its effect on cancer cell proliferation,apoptosis and migration.Methods:According to the previous sequencing projects,the gene PAGE4 with significant differential expression in cervical cancer has been screened.IHC and RT-qPCR were used to detect the PAGE4 in cervical cancer tissues and cell lines.Build and validate the overexpression vector of PAGE4 and then transfect it into SiHa and HeLa cell lines.Use CCK-8 assay,clone formation assay,flow cytometry,wound healing assay,Transwell assay,and Western blotting to explore the effect of PAGE4 in the proliferation,cell cycle,apoptosis,migration,and epithelial-mesenchymal transition of cervical cancer cells.The STRING database predicted the potential interaction molecule c-Jun of PAGE4.Its expression in cells overexpressing PAGE4 was detected by RT-qPCR.The role of c-Jun in PAGE4 mediated cervical cancer cell migration was preliminarily explored by silencing c-Jun and rescue experiments.Results:The sequencing analysis showed that PAGE4 was downregulated in cervical cancer by 457 folds.PAGE4 was downregulated in cervical cancer tissues and cervical cancer cell lines.Compared with the control group,there was no significant difference in cell proliferation,cell cycle,and apoptosis in the overexpression PAGE4 group.However,overexpression of PAGE4 inhibits the migration of cervical cancer cells,upregulates the expression of E-cadherin protein,and downregulates Vimentin protein.c-Jun reverses the effects of overexpression of PAGE4 on the migration and epithelial-mesenchymal transition of cervical cancer cells.Conclusion:Overexpression of PAGE4 can inhibit the migration and epithelial-mesenchymal transition of cervical cancer cells,and its mechanism may be related to the expression of c-Jun.In conclusion,PAGE4 may play a role in the metastasis of cervical cancer,and PAGE4 is expected to become a new target to inhibit tumor metastasis.

关 键 词：宫颈癌 PAGE4基因 生物信息学分析 转移 

分 类 号：R737.33[医药卫生—肿瘤]