上海交通大学学报（医学版）2025，Vol.45Issue(9)：1138-1148,11.DOI:10.3969/j.issn.1674-8115.2025.09.006
Zeste 12抑制基因在肝细胞癌中的功能及机制
Function and mechanism of suppressor of zeste 12 in hepatocellular carcinoma
摘要
Abstract
Objective·To explore the function and potential mechanism of suppressor of zeste 12(SUZ12)in hepatocellular carcinoma(HCC).Methods·The expression of SUZ12 in HCC patients was analyzed using R language in liver cancer datasets,and relevant survival curves were drawn.Stable knockdown of SUZ12 was established in the liver cancer cell lines LM3 and Huh7.The knockdown efficiency of SUZ12 was assessed using quantitative real-time PCR(qPCR)and Western blotting.Cell proliferation ability was assessed using CCK-8 assay and colony formation assay.Using the hydrodynamic tail vein injection(HTVI)method,Suz12 was knocked out in the livers of fully immunocompetent mice to explore its tumorigenic function in vivo.The molecular mechanism of SUZ12 regulating HCC was explored using The Cancer Genome Atlas(TCGA)database.R language was used to analyze the relationship between SUZ12 and the expression of cancer stem cell(CSC)markers as well as key glycolysis-related genes.Findings were validated in liver cancer cell lines and mouse tumor tissues.Results·The expression of SUZ12 in liver cancer tissues was higher than in adjacent non-tumor tissues,and its expression increased with higher tumor stage.HCC patients with high SUZ12 expression had poorer prognoses.In LM3 and Huh7 liver cancer cell lines,stable knockdown of SUZ12 reduced cell proliferation ability.In the de novo MYC/Trp53-/-mouse liver cancer model,tumor nodule number and size,and tumor burden in liver tissue were reduced after endogenous knockout of Suz12.TCGA analysis showed that high SUZ12 expression in HCC was enriched in multiple tumor proliferation-and metabolism-related pathways.The expression of SUZ12 was positively correlated with CSC markers and key genes in glycolysis pathway.The mRNA levels of CSC markers and key genes in glycolysis pathway were decreased in liver cancer cell lines with stable SUZ12 knockdown and Suz12 knockout mouse HCC tissues.Conclusion·The expression of SUZ12 is significantly increased in HCC patients and is associated with poor prognosis.Stable knockdown of SUZ12 weakens the proliferative ability of liver cancer cells.Knockout of Suz12 in mice in vivo can suppress the occurrence and development of HCC.The high expression of SUZ12 maintains the CSC pool,induces metabolic reprogramming,and promotes the occurrence and progression of HCC.SUZ12 can serve as a potential biomarker for poor prognosis and a novel target for potential therapeutic intervention in HCC.关键词
Zeste12抑制基因/肝细胞癌/水动力尾静脉注射/治疗靶点Key words
suppressor of zeste 12(SUZ12)/hepatocellular carcinoma(HCC)/hydrodynamic tail vein injection/therapeutic target分类
医药卫生引用本文复制引用
李倩玉,钱逸斐,李松玲,朱子俊,覃雯莉,刘艳丰,邱必军..Zeste 12抑制基因在肝细胞癌中的功能及机制[J].上海交通大学学报（医学版）,2025,45(9):1138-1148,11.基金项目
国家自然科学基金(82272684 （）
82241221) （）
上海市重中之重研究中心项目(2022ZZ01016) （2022ZZ01016）
上海市中央引导地方科技发展资金资助项目(YDZX20243100002002) （YDZX20243100002002）
上海交通大学医学院"双百人"项目(20221704). National Natural Science Foundation of China(82272684 （20221704）
82241221) （）
Project of Shanghai Key Research Center(2022ZZ01016) （2022ZZ01016）
Central Government Guidance Fund for Local Science and Technology Development of Shanghai(YDZX20243100002002) （YDZX20243100002002）
"Two-Hundred Talents"Program of Shanghai Jiao Tong University School of Medicine(20221704). （20221704）
