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

Abstract

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

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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