ERCC6L介导DNA修复和复制信号促进肝细胞癌增殖和转移

肝癌电子杂志 ›› 2025, Vol. 12 ›› Issue (3): 19-29.

ERCC6L介导DNA修复和复制信号促进肝细胞癌增殖和转移

李栋梁¹, 周保富¹, 杜朝刚¹, 吴静², 黄诚^3,*

1.安徽医科大学附属六安医院普通外科,安徽六安 237000;
2.安徽医科大学附属六安医院手术室,安徽六安 237000;
3.皖西卫生职业学院附属医院普通外科,安徽六安 237000

收稿日期:2025-04-09 出版日期:2025-09-30 发布日期:2025-11-03
通讯作者: ^*黄诚,E-mail：huangcheng@wahvc.edu.cn
基金资助:
安徽省卫生健康科研项目(AHWJ2024Ab0056); 六安市科学技术局基金项目（2023lakj004）

ERCC6L mediates DNA repair and replication signaling to promote hepatocellular carcinoma proliferation and metastasis

Li Dongliang¹, Zhou Baofu¹, Du Chaogang¹, Wu Jing², Huang Cheng^3,*

1. Department of General Surgery, Lu'an Hospital of Anhui Medical University, Lu'an 237000, Anhui, China;
2. Operating Room, Lu'an Hospital of Anhui Medical University, Lu'an 237000, Anhui, China;
3. Department of General Surgery, Affiliated Hospital of West Anhui Health Vocational College, Lu'an 237000, Anhui, China

Received:2025-04-09 Online:2025-09-30 Published:2025-11-03
Contact: ^* Huang Cheng,E-mail: huangcheng@wahvc.edu.cn

摘要/Abstract

摘要： 目的: 探索ERCC6L基因在肝细胞癌（HCC）增殖和转移中的作用机制。
方法: 通过UALCAN、人类蛋白图谱(HPA)、基因表达谱交互分析(GEPIA)、临床生信之家、Kaplan-Meier plot和甲基化数据可视化工具(SMART)数据库、免疫组织化学分析HCC中ERCC6L表达特征和预后差异以及DNA甲基化水平。通过体内和体外实验分析ERCC6L表达对HCC细胞增殖、迁移及侵袭影响。通过流式细胞仪分析ERCC6L对HCC细胞周期影响。通过功能富集和蛋白质印迹法分析ERCC6L对HCC细胞中的DNA修复和复制信号（RRM1、RRM2、POLE2和LIG1）影响。
结果: ERCC6L的mRNA和蛋白质水平在HCC组织中均表达上调（均P<0.05）。ERCC6L高表达的HCC患者总生存率低于低表达患者（P<0.05）。ERCC6L在HCC患者中显示出低甲基化状态,包括cg01004805、cg12747864、cg09743261、cg05279113。敲降ERCC6L能抑制HCC细胞活力、增殖、迁移和侵袭能力,降低HCC生长速度（均P<0.05）。ERCC6L的KEGG信号通路主要富集在细胞周期、DNA复制和Fanconi贫血通路中。敲降ERCC6L表达能诱导HCC细胞G₀/G₁期停滞,降低RRM1、RRM2、POLE2和LIG1蛋白表达水平（均P<0.05）。
结论: ERCC6L在HCC患者中高表达并介导更差预后,其潜在机制通过介导DNA修复与DNA复制信号。

关键词: 肝细胞癌, ERCC6L基因, DNA修复, DNA复制, 细胞增殖, 细胞迁移, 细胞侵袭

Abstract: Objective: To explore the mechanism of ERCC6L gene in hepatocellular carcinoma(HCC).
Methods: The expression and prognostic differences of ERCC6L and DNA methylation levels in HCC cells were analyzed by public databases and immunohistochemistry; the effects of ERCC6L expression on HCC cells proliferation, transfer and invasion were analyzed by in vivo and in vitro experiments, and the cell cycle effects of ERCC6L on HCC cells were analyzed by flow cytometry. The effects of ERCC6L on DNA repair and replication signals (RRM1,RRM2,POLE2 and LIG1) in HCC cells were analyzed by functional enrichment and protein immunoblotting experiments.
Results: ERCC6L mRNA and protein levels were up-regulated in HCC tissues (all P<0.05).The overall survival rate of HCC patients with high expression of ERCC6L was lower than that of patients with low expression (P<0.05). ERCC6L showed hypomethylation status in HCC patients,including cg01004805, cg12747864, cg09743261, cg05279113. Knockdown of ERCC6L inhibited HCC cell viability, proliferation, migration and invasive ability, and reduced HCC tumor growth (all P<0.05). The KEGG signaling pathway of ERCC6L was mainly enriched in cell cycle,DNA replication and Fanconi anemia pathways. Knockdown of ERCC6L expression induced G₀/G₁ phase arrest in HCC cells and decreased the levels of RRM1,RRM2,POLE2 and LIG1 protein expression (all P<0.05).
Conclusion: ERCC6L is highly expressed in HCC patients and mediates worse prognosis by a potential mechanism through mediating DNA repair and replication signaling.

Key words: Hepatocellular carcinoma, ERCC6L gene, DNA repair, DNA replication, Cells proliferation, Cells transfer, Cells invasion

李栋梁, 周保富, 杜朝刚, 吴静, 黄诚. ERCC6L介导DNA修复和复制信号促进肝细胞癌增殖和转移[J]. 肝癌电子杂志, 2025, 12(3): 19-29.

Li Dongliang, Zhou Baofu, Du Chaogang, Wu Jing, Huang Cheng. ERCC6L mediates DNA repair and replication signaling to promote hepatocellular carcinoma proliferation and metastasis[J]. Electronic Journal of Liver Tumor, 2025, 12(3): 19-29.

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