Effect of ubiquitin-conjugating enzyme E2C on stem cell-like properties of hepatocellular carcinoma cells and its mechanisms
10.3969/j.issn.1000-4718.2025.00.016
- VernacularTitle:泛素缀合酶E2C对肝癌细胞干细胞样特性的影响及其机制
- Author:
Tingjun LIU
1
;
Junru WU
;
Liuyan CHEN
;
Yuchen LIN
;
Keke ZHANG
;
Jian HONG
;
Souqi LIAO
Author Information
1. 暨南大学基础医学与公共卫生学院机能学实验教学中心,广东 广州 510632
- Publication Type:Journal Article
- Keywords:
ubiquitin-conjugating enzyme E2C;
hepatocellular carcinoma;
liver cancer stem cells;
signal transducer and activator of transcription 3
- From:
Chinese Journal of Pathophysiology
2025;41(6):1055-1065
- CountryChina
- Language:Chinese
-
Abstract:
AIM:This study aims to investigate the expression and prognostic value of ubiquitin-conjugating enzyme E2C(UBE2C)in hepatocellular carcinoma(HCC),and to explore its impact on cancer stemness and the regulato-ry mechanisms.METHODS:(1)The TCGA and GEO databases were used to analyze UBE2C mRNA expression levels in HCC tissues and their correlation with prognosis using bioinformatics techniques,and these findings were further vali-dated in postoperative specimens from 107 HCC patients.The GEPIA database was used to analyze the correlation be-tween UBE2C and steroid receptor coactivator(SRC).(2)The CCK8,colony formation,wound healing,and spheroid formation assays were used to assess the effects of UBE2C on HCC cell proliferation,migration,and stemness.The inter-action between UBE2C and signal transducer and activator of transcription 3(STAT3),as well as its regulatory mecha-nism,was examined by Western blot and co-immunoprecipitation assays.(3)The subcutaneous xenograft model in nude mice was employed to validate the role of UBE2C in tumor growth in vivo.RESULTS:(1)Bioinformatics analysis re-vealed that UBE2C expression was significantly up-regulated in HCC tissues compared with adjacent normal tissues(P<0.05 in TCGA,and P<0.01 in GEO).Consistently,analysis of HCC specimens confirmed that high UBE2C expression was associated with shortened overall survival and disease-free survival of HCC patients(P<0.05).Furthermore,analysis using the GEPIA database revealed a positive correlation between UBE2C and SRC(P<0.01).(2)In vitro experiments demonstrated that UBE2C significantly promotes the proliferation and migration of HCC cells.Based on these findings,we presumed that UBE2C may regulate the phosphorylation of STAT3 at the Y705 site by modulating SRC activity,thereby in-fluencing the stemness characteristics of tumor cells.(3)In vivo experiments further confirmed that UBE2C inhibition sig-nificantly suppressed tumor growth.CONCLUSION:The UBE2C promoted proliferation and migration of HCC cells and regulated the stemness of HCC cells by interacting with STAT3.
