2. Academic Validation
  3. UBE2Q2 promotes tumor progression and glycolysis of hepatocellular carcinoma through NF-κB/HIF1α signal pathway

UBE2Q2 promotes tumor progression and glycolysis of hepatocellular carcinoma through NF-κB/HIF1α signal pathway

  • Cell Oncol (Dordr). 2025 Jan 20. doi: 10.1007/s13402-025-01037-w.
Xiaoling Wu # 1 2 3,  Yiran Chen # 1 4,  Wenzhi He 1 5,  Ye Yao 1 5,  Yingyi Liu 1 5,  Peng Xia 1 5,  Hao Zhang 1 5,  Xiaomian Li 1 5,  Yonghua Guo 1 5,  Xi Chen 6 7,  Weijie Ma 8 9,  Yufeng Yuan 10 11
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, PR China.
  • 2 Department of Liver Surgery, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Zhongshan Hospital, Liver Cancer Institute, Fudan University, Shanghai, China.
  • 3 Research Unit of Liver Cancer Recurrence and Metastasis, Chinese Academy of Medical Sciences, Beijing, China.
  • 4 Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, China.
  • 5 Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, PR China.
  • 6 Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, PR China. chenxi2022@whu.edu.cn.
  • 7 Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, PR China. chenxi2022@whu.edu.cn.
  • 8 Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, PR China. mawj1990@whu.edu.cn.
  • 9 Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, PR China. mawj1990@whu.edu.cn.
  • 10 Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan, Hubei, 430071, PR China. yuanyf1971@whu.edu.cn.
  • 11 Clinical Medicine Research Center for Minimally Invasive Procedure of Hepatobiliary & Pancreatic Diseases of Hubei Province, Wuhan, Hubei, 430071, PR China. yuanyf1971@whu.edu.cn.
  • # Contributed equally.
PMID: 39833608 DOI: 10.1007/s13402-025-01037-w
Abstract

Purpose: Metabolic reprogramming, particularly the Warburg effect, plays a crucial role in the onset and progression of tumors. The ubiquitin-conjugating Enzyme E2 Q2 (UBE2Q2) has been identified overexpressed in hepatocellular carcinoma (HCC). Our aim was to determine if UBE2Q2 plays a role in regulating glycolysis, contributing to the carcinogenesis of HCC.

Methods: Bioinformatics analysis, western blot and qPCR were used to detect the expression of UBE2Q2. Functional experiments, proteomics analysis and subcutaneous tumors were constructed to find the biological function of UBE2Q2 in HCC. Co-immunoprecipitation, western blot and ubiquitination assays were used to identify the mechanisms involved.

Results: We found a significant association between high UBE2Q2 expression and poor prognosis in HCC patients. Functionally, UBE2Q2 was shown to advance tumor progression in HCC through both in vitro assays and in vivo assessments. Proteomics analysis and glycolysis stress tests corroborated an increase in glycolytic activity due to UBE2Q2. Our findings reveal that UBE2Q2 augments glycolysis by boosting the transcription levels of hypoxia-inducible factor 1α (HIF1α), primarily through the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. At the molecular level, UBE2Q2 interaction with baculoviral IAP repeat-containing 2 (cIAP1) orchestrates the K63-linked ubiquitination of receptor-interacting serine/threonine-protein kinase 1 (RIP1), which in turn, activates the NF-κB signaling pathway.

Conclusions: Our investigation reveals that UBE2Q2 regulates the glycolysis in HCC through modulation of the NF-κB/HIF1α signaling pathway, pinpointing UBE2Q2 as a promising therapeutic target for the disease.

Keywords

HIF1α; Hepatocellular carcinoma; NF-κB signaling pathway; UBE2Q2; Ubiquitination.

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