biostudies-literatureZhou Bthe Science and Technology Research Program of Chongqing Municipal Education Commission8869https://www.ebi.ac.uk/biostudies/studies/S-EPMC11909175biostudies-literatureUnknown15(1)Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, characterized by a high rate of postoperative recurrence and poor long-term survival outcomes. Structural maintenance of chromosome 4 (SMC4) is frequently overexpressed in various types of cancer and plays a pivotal role in tumor cell growth, migration, and invasion. Bioinformatics analysis has revealed a significant correlation between the tumor-node metastasis (TNM) stage (P < 0.01) and SMC4 expression (P < 0.05), and SMC4 was associated with poor prognosis in HCC. Furthermore, SMC4 was identified as an independent prognostic factor for HCC. Ubiquitin-specific peptidase 39 (USP39) was found whether the regulation was observed to affect protein synthesis or stability through bioinformatics analysis and immunoprScientific reportsUSP39/SMC4 promotes hepatoma cell proliferation and 5-FU resistance.PMC11909175KJZD-K202412801Li JChen JZhou BZhang HWu SChen GLuo YfalseUSP39/SMC4 promotes hepatoma cell proliferation and 5-FU resistance.Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality, characterized by a high rate of postoperative recurrence and poor long-term survival outcomes. Structural maintenance of chromosome 4 (SMC4) is frequently overexpressed in various types of cancer and plays a pivotal role in tumor cell growth, migration, and invasion. Bioinformatics analysis has revealed a significant correlation between the tumor-node metastasis (TNM) stage (P < 0.01) and SMC4 expression (P < 0.05), and SMC4 was associated with poor prognosis in HCC. Furthermore, SMC4 was identified as an independent prognostic factor for HCC. Ubiquitin-specific peptidase 39 (USP39) was found whether the regulation was observed to affect protein synthesis or stability through bioinformatics analysis and immunopr2025-01-01T00:00:00Z2025 Mar2026-06-03T02:32:38.066Z2025-04-04T00:32:37.518ZS-EPMC119091754008733110.1038/s41598-025-93029-x