Open Access

ARTICLE

Comprehensive Analysis of the Expression Levels and Prognostic Values of SENP Family Genes in Liver Hepatocellular Carcinoma

Shuyan Kong^1,#, Danting Li^1,#, Haonan Meng^1,#, Haoxiang Zhang¹, Xiaochun Jiang¹, Peilin Zheng², Shoujun Huang^1,*

1 Anhui Province Key Laboratory of Resource Insect Biology and Innovative Utilization, School of Life Sciences, Anhui Agricultural University, Hefei, 230036, China
2 Department of General Practice, People’s Hospital of Longhua, Shenzhen, 518109, China

* Corresponding Author: Shoujun Huang. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Genetic Biomarkers of Cancer: Insights into Molecular and Cellular Mechanisms)

BIOCELL 2025, 49(8), 1481-1504. https://doi.org/10.32604/biocell.2025.066205

Received 01 April 2025; Accepted 08 July 2025; Issue published 29 August 2025

Abstract

Background: Small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) cleave the isopeptidic bond between SUMO1/2/3 and protein substrates, thus regulating the structure, activity, and lifetime of a variety of proteins. Recently, accumulating evidence has suggested that SENPs play a role in the initiation and progression of human cancers. Nevertheless, the potential role of the SENP family of proteins in liver cancer has yet to be fully elucidated. Methods: This study conducted a comprehensive bioinformatics analysis of the SENP family in liver cancer, including differential expression profiling, survival analysis, mutation and copy number variations (CNVs) assessment, immune infiltration and drug sensitivity correlation, functional enrichment analyses using data from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), LinkedOmics, and other public databases. Furthermore, we performed in vitro experiments using Huh-7 and Hep-3B cell lines to investigate the functional roles of SENP1 and SENP3 in hepatocellular carcinoma cell proliferation, colony formation, and migration. Results: Our results indicated that SENP1, 3, and 7 were significantly overexpressed in liver hepatocellular carcinoma (LIHC). Elevated expressions of SENP1, 3, and 7 are positively correlated with poor overall survival (OS) in LIHC patients. In addition, SENP1, 3, and 7 expressions are related to immune infiltration and drug sensitivity. SENP1, 3, and 7 co-expressed genes were enriched in mitochondrial function, ribosomal translation, and cell cycle control. Conclusion: SENP1, 3, and 7 are prognostic biomarkers and potential therapeutic targets for LIHC. Knockdown of SENP1 and SENP3 inhibited the proliferation, clonogenicity, and migration of hepatocellular carcinoma cells.

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Supplementary Material

Supplementary Material File

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