摘要
目的:探究DNAJC2在肝细胞癌中的作用,以及对肝癌细胞增殖、迁移、侵袭和凋亡能力的影响。方法:基于生物信息学分析DNAJC2在肝癌中的表达和预后作用,使用TCGA数据库对DNAJC2的正、负相关基因进行KEGG富集分析,GDSC数据库分析DNAJC2表达量不同时药物敏感性的差异。CCK-8和集落形成实验、Transwell和划痕实验、Hoechst和JC-1实验检测敲低DNAJC2对肝癌MHCC97H细胞增殖能力、细胞迁移和侵袭能力、细胞凋亡能力的影响。结果:DNAJC2在肝癌中高表达并与患者的预后显著相关。DNAJC2的正相关基因与主要富集于核质转运、泛素介导的蛋白质降解等通路,负相关基因与补体和凝血级联反应有关。DNAJC2高表达组对索拉菲尼和舒尼替尼更敏感。细胞实验表明,敲低DNAJC2可抑制肝癌细胞MHCC97H的增殖、迁移及侵袭,并促进其凋亡。结论:DNAJC2在肝癌中高表达并具有良好的预后价值,且高水平DNAJC2对索拉菲尼敏感;在肝癌中可能与核质转运、泛素介导的蛋白质降解、补体和凝血级联反应等信号通路相关;敲低DNAJC2能抑制肝癌细胞恶性行为。
Objective:To explore the role of DNAJC2 in hepatocellular carcinoma and its effects on proliferation,migration,invasion and apoptosis of hepatocellular carcinoma cells.Methods:Based on bioinformatics analysis,the expression and prognostic role of DNAJC2 in hepatocellular carcinoma were investigated.The KEGG enrichment analysis was conducted on DNAJC2's positive and negative correlated genes using TCGA database.The GDSC database was used to analyze drug sensitivity based on DNAJC2 expression.CCK-8 assay and colony formation assay,Transwell and scratch assay,Hoechst and JC-1 assay were performed to assess the effects of DNAJC2 knockdown on hepatocellular carcinoma MHCC97H cell proliferation,migration,invasion and apoptosis.Results:DNAJC2 was highly expressed in hepatocellular carcinoma and significantly correlated with patient prognosis.KEGG pathway enrichment analysis revealed that positively correlated genes of DNAJC2 were mainly enriched in pathways related to nucleocytoplasmic transport,and ubiquitin-mediated protein degradation,while negatively correlated genes were associated with complement and coagulation cascades.The high expression group of DNAJC2 showed higher sensitivity to sorafenib and sunitinib.Cell experiments showed that knockdown of DNAJC2 significantly reduced the proliferation,migration,and invasion,and promoted apoptosis of MHCC97H cells.Conclusion:DNAJC2 is highly expressed in hepatocellular carcinoma and has a favorable prognostic value.High levels of DNAJC2 are associated with increased sensitivity to sorafenib.In hepatocellular carcinoma,DNAJC2 may be involved in signaling pathways related to nucleocytoplasmic transport,ubiquitin-mediated protein degradation,complement and coagulation cascades.Knockdown of DNAJC2 can suppress the malignant behavior of hepatocellular carcinoma cells.
作者
徐子云
范玉纯
韦万硕
张朝升
张林莉
吴桐
蒋利和
XU Ziyun;FAN Yuchun;WEI Wanshuo;ZHANG Chaosheng;ZHANG Linli;WU Tong;JIANG Lihe(School of Basic Medicine,Youjiang Medical College for Nationalities,Guangxi Baise 533000,China;Medical College of Guangxi University,Guangxi Nanning 530004,China;School of Clinical Medicine,Youjiang Medical College for Nationalities,Guangxi Baise 533000,China)
出处
《现代肿瘤医学》
CAS
2024年第8期1375-1381,共7页
Journal of Modern Oncology
基金
2022年国家级大学生创新创业训练计划项目(编号:202210599007,202210599005)
广西医学遗传与基因组学研究重点实验室开放课题(编号:GXKMGG202201)
广西南宁市青秀区重点研发项目(编号:2020023)
右江民族医学院高层次引进人才项目(编号:yy2021sk002)。
关键词
肝癌
DNAJC2
生物信息学分析
细胞实验
hepatocellular carcinoma
DNAJC2
bioinformatics analysis
cell experiments
