A bioinformatics study on the mechanism of ubiquitin C-terminal hydrolase L5 in regulating downstream targets of hepatocellular carcinoma

LIU Ziyao; SHEN Jie; XIE Zhengyao

doi:10.3969/j.issn.1009-0460.2025.04.002

Abstract：Objective To explore the expression characteristics,target binding patterns and regulatory mechanisms of ubiquitin C-terminal hydrolase L5(UCHL5)in hepatocellular carcinoma using bioinformatics methods,and to evaluate its potential as a therapeutic target and a predictive biomarker for immunotherapy efficacy.Methods The expression of UCHL5 in different subgroups of liver cancer patients was analyzed using the UALCAN database.Immune infiltration and tumor mutation burden were analyzed using CIBERSORT and maftools.Kaplan-Meier survival analysis was performed using the survival and survminer packages.The binding of UCHL5 to its targets was analyzed using eCLIP data.In addition,RNA-seq data from UCHL5 knockdown experiments were used to investigate the regulatory mechanisms of UCHL5 on target gene transcription.Results The expression level of UCHL5 in liver cancer tissues was significantly elevated(P<0.0001),with significant differences between stage 2 and stage 3 liver cancers(P<0.05).The expression of UCHL5 also varied significantly between liver cancer tissues with and without TP53 mutations(P<0.0001).In the low UCHL5 expression group,plasma cells and regulatory T cells were significantly more abundant than in the high expression group,while eosinophils and neutrophils were significantly lower(P<0.05).The CD8+T cell population was significantly higher in the low UCHL5 expression group than in the high expression group(P<0.001).The tumor mutation burden was significantly higher in the high UCHL5 expression group than in the low expression group(P<0.05).In the HepG2 cells,UCHL5 primarily binds to the exonic regions of target genes,participating in RNA splicing regulation and stress granule formation.After UCHL5 knockdown,the expression of several target genes associated with liver cancer progression changed significantly,indicating that UCHL5 may promote the development of liver cancer cells by regulating these genes.Conclusion This study elucidates the important role and potential mechanisms of UCHL5 in liver cancer,highlighting its clinical value as a potential therapeutic target and predictive biomarker for immunotherapy efficacy.