转录因子YY1在肝细胞癌中的表达和功能研究

doi:10.3969/j.issn.1009-976X.2021.01.008

摘要/Abstract

摘要： 目的探讨转录因子YY1在肝细胞癌进展中的作用并揭示其发挥功能的潜在分子机制。方法生物信息学分析TCGA、GEO及ICGC公共数据库中肝癌组织中YY1的表达及其与临床病理特征及预后的关系。并在本院收集的肝癌石蜡切片行免疫组化实验验证。采用CCK-8、Edu染色及克隆形成实验探讨YY1对肝癌细胞增殖能力的影响,采用Transwell实验探讨YY1对肝癌细胞迁移及侵袭能力的影响。通过基因集富集分析、基因共表达分析和蛋白质互作网络分析探讨YY1发挥功能的潜在分子机制。结果分析TCGA-LIHC、GSE14520、GSE25097及ICGC-LIRI-JP肝细胞癌转录组数据,结果显示YY1在肝癌组织中的表达显著高于癌旁组织,高表达YY1预示更短的总体生存;YY1表达与患者的肿瘤体积、肿瘤分期及肿瘤病理学分级正相关。免疫组化验证实验中证实肝癌组织YY1显著高于癌旁组织;体外细胞实验结果显示,敲降YY1表达后,肝癌细胞的增殖、迁移及侵袭能力显著降低,而过表达YY1后,肝癌细胞的增殖、迁移及侵袭能力则显著增加。基因集富集分析发现高表达YY1的患者中与肿瘤进展相关信号通路高度富集,共表达基因及蛋白质互作网络分析发现,YY1与FKBP3、RBBP7、H2AFV、H2AFZ、ACTL6A、PAXIP1、NCOA6、SUZ12等8个共表达基因存在高度可信的相互作用网络。结论 YY1在肝细胞癌中高表达,与不良预后相关。发挥癌基因作用,可能与其促肝癌细胞增殖、迁移及侵袭能力有关;YY1在肝细胞癌中的表达能指示总体生存,可作为潜在的肝癌生物标志物及药物治疗靶点。

关键词: YY1, 肝癌, 预后, 增殖, 迁移, 侵袭

Abstract: Objective To investigate the function of transcription factor YY1 in the progression of hepatocellular carcinoma（HCC） and reveal the potential molecular mechanisms. Methods The expression of YY1 in HCC and its relationships with clinicopathological characteristics and prognosis were analyzed in TCGA, GEO and ICGC databases. Immunohistochemical experiments were used to detect the expression of YY1 in tumor and non-tumor tissues collected in our hospital. The effect of YY1 on the proliferation of HCC cells was studied by CCK-8 assay, Edu staining and clone formation experiments. The migration and invasion abilities of HCC cells were measured by Transwell assay. Gene set enrichment analysis, gene co-expression analysis and protein interaction network analysis were conducted to explore the potential molecular mechanism of YY1 function. Results Compared with non-tumor tissues, YY1 expressions were significantly up-regulated in HCC tissues in TCGA, GEO and ICGC databases. Higher YY1 expression indicated poorer survival outcome. Moreover, YY1 expression level was positively correlated with the tumor volume, tumor stage and tumor pathological grade in HCC patients. Immunochemistry assay verified YY1 was significantly up-regulated in tumor tissues in our HCC cohort. Further in vitro experiments found YY1 knockdown or overexpression can inhibit or promote the proliferation, migration and invasion abilities of HCC cells. Gene set enrichment analysis found that the tumor progression related-signaling pathways were significantly enriched in patients with high expression of YY1. Co-expressed gene and protein interaction network analysis indicated YY1 had a highly credible interaction network with FKBP3, RBBP7, H2AFV, H2AFZ, ACTL6A, PAXIP1, NCOA6, SUZ12. Conclusion YY1 was overexpressed in HCC and associated with poor prognosis. YY1 exerted an oncogene effect through promoting the proliferation, migration and invasion abilities of HCC cells and might be a potential drug therapy target for HCC patients.

Key words: YY1, hepatocellular carcinoma, prognosis, migration, invasion

中图分类号:

R735.7

黄贻培, 罗伟鑫, 许磊波. 转录因子YY1在肝细胞癌中的表达和功能研究[J]. 岭南现代临床外科, 2021, 21(01): 44-52.

HUANG Yi-pei, LUO Wei-xin, XU Lei-bo. Expression and function of transcription factor YY1 in hepatocellular carcinoma[J]. Lingnan Modern Clinics In Surgery, 2021, 21(01): 44-52.

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