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Updated: Feb 16, 2026

Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
UBE2C is involved in the functions of ECRG4 on esophageal squamous cell carcinoma
Linwei Li1, Xiaoyan Li1, Wenyu Wang1
1Oncology Department, Henan Provincial People's Hospital (Zhengzhou University People's Hospital, Henan University People's Hospital), Zhengzhou, Henan 450003, PR China.
Background:
Esophageal cancerrelated gene 4 (ECRG4) is down-regulated in esophageal squamous-cell carcinoma (ESCC) and inhibits the tumorigenicity of ESCC cells. Ubiquitin conjugating enzyme E2 (UBE2C), an E2 ubiquitin-conjugating enzyme, is upregulated in numerous human cancers, including ESCC.
Methods:
mRNA and protein expression was determined by real-time PCR and western blotting analysis, respectively. Cell apoptosis was assessed by Annexin V-fluorescein isothiocyanate staining and flow cytometry analysis.
Results:
By analyzing previous quantitative proteomics data on EC9706 cells, we found that UBE2C was significantly down-regulated in ECRG4 overexpressed cells. Western blotting analysis validated the proteomics results in both EC9706 and EC-18 cells. In addition, Pearson's correlation analysis demonstrated a negative correlation between the mRNA levels of ECRG4 and UBE2C in ESCC tissues. Then, we found that Nuclear Factor-κB (NF-κB) inhibitor, pyrriolidine-dithiocarbamate (PDTC), could inhibit NF-κB p65 nuclear translocation and UBE2C expression, which was partially reversed by ECRG4 silence. More importantly, UBE2C knockdown in TE-1 cells significantly inhibited cell proliferation and induced cell apoptosis, which was partially reversed by ECRG4 knockdown.
Conclusions:
ECRG4 down-regulated UBE2C expression in ESCC cells via NF-κB signaling. UBE2C was involved in the anti-proliferative and pro-apoptotic functions of ECRG4 in ESCC cells.
Insights
Esophageal cancer-related gene 4 (ECRG4) suppresses esophageal squamous-cell carcinoma (ESCC) by down-regulating UBE2C through NF-κB signaling. ECRG4
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Esophageal cancer-related gene 4 (ECRG4) is downregulated in esophageal squamous-cell carcinoma (ESCC), inhibiting tumor growth.
- Ubiquitin conjugating enzyme E2 (UBE2C) is upregulated in various human cancers, including ESCC.
Purpose of the Study:
- To investigate the regulatory relationship between ECRG4 and UBE2C in ESCC.
- To elucidate the underlying molecular mechanisms of ECRG4's tumor-suppressive function in ESCC.
Main Methods:
- Quantitative proteomics, Western blotting, and real-time PCR were used to assess protein and mRNA expression.
- Cell apoptosis was analyzed using Annexin V/flow cytometry.
- NF-κB signaling pathway activity was evaluated using an NF-κB inhibitor.
Main Results:
- ECRG4 overexpression led to decreased UBE2C expression in ESCC cells.
- A negative correlation was observed between ECRG4 and UBE2C mRNA levels in ESCC tissues.
- ECRG4 regulated UBE2C expression via the NF-κB signaling pathway.
- UBE2C knockdown mimicked and partially reversed the anti-proliferative and pro-apoptotic effects of ECRG4.
Conclusions:
- ECRG4 downregulates UBE2C expression in ESCC cells through the NF-κB signaling pathway.
- UBE2C plays a crucial role in mediating the anti-proliferative and pro-apoptotic effects of ECRG4 in ESCC.
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