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敲低CCAAT/增强子结合蛋白β促进肝癌细胞的增殖和迁移

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近年来已有研究表明,C/EBP β在肝癌的发生发展中发挥重要的作用,但其具体分子调控机制尚不清楚。本研究通过分析GEO数据库和Kaplan-Meier Plotter数据库发现,C/EBP β mRNA在肝癌中低表达(P<0。05),且其低表达与肝癌患者预后密切相关。进一步,通过功能富集分析和TIMER数据库分析显示,C/EBP β主要参与细胞周期、DNA转录等生物学过程,且C/EBP β表达水平与CD4+T细胞和巨噬细胞的免疫浸润具有较强的相关性(P<0。05)。为了进一步研究C/EBPβ对肝癌细胞增殖和迁移的影响。在肝癌细胞中瞬时转染C/EBP β siRNA,将其分为si-NC组和siC/EBP β组。通过qRT-PCR、Western印迹检测肝癌细胞中C/EBP β在mRNA和蛋白质水平均显著降低(P<0。05);通过MTT检测、平板克隆形成实验和5-乙炔基-2-脱氧尿嘧啶核苷(Edu)实验证实,敲低C/EBP β促进肝癌细胞的增殖(P<0。05);Transwell和划痕实验证实,敲低C/EBP β促进肝癌细胞的迁移;Western印迹法检测敲低C/EBP β对肝癌细胞内迁移相关蛋白质(E-cadherin、N-cadherin)以及Wnt/β-catenin信号通路蛋白质表达的影响,结果表明,敲低C/EBP β促进肝癌细胞EMT上皮间质转化,并能激活Wnt/β-catenin信号通路的基因表达(P<0。05)。综上所述,C/EBP β在肝癌组织中低表达且与患者生存预后成正相关。敲低C/EBP β可能通过激活Wnt/β-catenin信号通络促进肝癌细胞的增殖、迁移和上皮间质转化,为C/EBP β在肝癌的发生发展中的作用提供了依据,可能是一个肝癌诊治过程中的潜在靶点。
Knockdown of C/EBP β Promotes the Proliferation and Migration of Hepatocellular Carcinoma Cells
In recent years,studies have shown that C/EBP β plays an important role in the occurrence and development of liver cancer,but its specific molecular regulatory mechanism is still unclear.In this study,we analyzed the GEO database and the Kaplan-Meier Plotter database and found that the mRNA expression of C/EBP β was low in hepatocellular carcinoma(HCC)cells(P<0.05),and its low ex-pression was closely related to the prognosis of HCC patients.Furthermore,functional enrichment analy-sis and TIMER database analysis showed that C/EBP β was mainly involved in biological processes such as cell cycle and DNA transcription,and the expression level of C/EBP β had a strong correlation with the immune infiltration of CD4+T cells and macrophages(P<0.05).To further investigate the effect of C/EBP β on the proliferation and migration of HCC cells.In the experiment,HCC cells were transiently transfected with C/EBP β siRNA and divided into si-NC group and siC/EBP β group.The mRNA and protein levels of C/EBP β in HCC cells were significantly reduced by qRT-PCR and Western blot(P<0.05),and MTT detection,plate cloning assay,and 5-ethynyl-2'deoxyuracil nucleoside(Edu)assay confirmed that knockdown of C/EBP β promotes the proliferation of HCC cells(P<0.05);Transwell and scratch assays confirmed that knockdown of C/EBP β promote the migration of HCC cells;Western blot method was used to detect the effect of knockdown of C/EBP β on the expression of migration-related proteins(E-cadherin,N-cadherin)and Wnt/β-catenin signaling pathway proteins.The results showed that knockdown of C/EBP β promotes epithelial-mesenchymal transition(EMT)and activates gene ex-pression of Wnt/β-catenin signaling pathway in HCC cells(P<0.05).In conclusion,C/EBP β was un-derexpressed in HCC tissues and was positively correlated with the survival prognosis of patients.Knock-down of C/EBP β may promote the proliferation,migration,and epithelial-mesenchymal transformation of HCC cells by activating the Wnt/β-catenin signaling pathway,which provides a basis for the role of C/EBP β in the occurrence and development of HCC and may be a potential target in the diagnosis and treatment of HCC.

hepatocellular carcinoma(HCC)cell proliferationcell migrationCCAAT/enhancer binding protein β(C/EBP β)

陈利荣、刘玉玲、贾艳梅、梁紫微、李佳佳

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山西医科大学汾阳学院医学检验系,山西汾阳 032200

太原理工大学生物医学工程学院,太原 030000

山西医科大学研究生学院,太原 030000

肝癌 细胞增殖 细胞迁移 CCAAT/增强子结合蛋白β

山西省吕梁市科学技术局社会发展领域重点研发计划项目国家自然科学基金项目

2020SHFZ3482103147

2024

中国生物化学与分子生物学报
中国生物化学与分子生物学会 北京大学

中国生物化学与分子生物学报

CSTPCD北大核心
影响因子:0.617
ISSN:1007-7626
年,卷(期):2024.40(6)
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