Related Experiment Video
Updated: May 8, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Inhibiting UHRF1 expression enhances radiosensitivity in human esophageal squamous cell carcinoma
Congrong Yang1, Yadi Wang, Fuli Zhang
1Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, China.
Abstract:
Radiotherapy is an effective treatment for some esophageal cancers, but the molecular mechanisms of radiosensitivity remain unknown. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is a novel nuclear protein which is overexpressed in various cancers but not yet examined in esophageal squamous cell carcinoma (ESCC). The correlation between UHRF1 and the radioresistance in ESCC is still unclear. In the present study, the expression of UHRF1 was examined by immunohistochemistry in specimens of ESCC patients treated with radiotherapy. The results showed that UHRF1 was significantly overexpressed in ESCC specimens. Overexpression of UHRF1 correlated significantly with advanced T-stage, positive lymph node metastasis and poor differentiation. In addition, UHRF1 was associated with radiotherapy response, in which overexpression of UHRF1 was observed more frequently in the radioresistant group than in the effective group. At the molecular level, inhibition of UHRF1 by lentivirus-mediated shRNA targeting UHRF1 increased the radiosensitivity and apoptosis, while decreased radiation-induced G2/M phase arrest in TE-1 cells. Moreover, inhibition of UHRF1 resulted in higher residual γH2AX expression after irradiation, but not initial γH2AX. Further study showed that inhibition of UHRF1 down-regulated the endogenous expressions of DNA repair protein Ku70 and Ku80 in TE-1 cells, and significantly inhibited the increase of these proteins after irradiation. Above all, our data suggested that UHRF1 might play an important role in radioresistance of ESCC, and inhibition of UHRF1 can increase the radiosensitivity of TE-1 cells by altering cell cycle progression, enhancing apoptosis, and decreasing DNA damage repair capacity.
Insights
Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) overexpression is linked to radioresistance in esophageal squamous cell carcinoma (ESCC). Inhibiting UHRF1 enhances radiosensitivity by promoting apoptosis and reducing DNA repair.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Radiotherapy is a key treatment for esophageal cancers, but its effectiveness is limited by radioresistance.
- The molecular underpinnings of radioresistance in esophageal squamous cell carcinoma (ESCC) are not fully understood.
- Ubiquitin-like with PHD and ring finger domains 1 (UHRF1), a nuclear protein overexpressed in many cancers, has not been investigated in ESCC radioresistance.
Purpose of the Study:
- To investigate the role of UHRF1 in the radioresistance of ESCC.
- To determine the correlation between UHRF1 expression and patient response to radiotherapy.
- To elucidate the molecular mechanisms by which UHRF1 influences radiosensitivity in ESCC cells.
Main Methods:
- Immunohistochemistry was used to assess UHRF1 expression in ESCC patient specimens treated with radiotherapy.
- Lentivirus-mediated shRNA was employed to inhibit UHRF1 expression in TE-1 ESCC cells.
- Cell cycle progression, apoptosis, and DNA damage repair markers (γH2AX, Ku70, Ku80) were analyzed following UHRF1 inhibition and irradiation.
Main Results:
- UHRF1 was significantly overexpressed in ESCC specimens and correlated with advanced T-stage, lymph node metastasis, and poor differentiation.
- Overexpression of UHRF1 was more frequent in radioresistant ESCC cases compared to those sensitive to radiotherapy.
- Inhibition of UHRF1 in TE-1 cells increased radiosensitivity and apoptosis, reduced G2/M phase arrest, elevated residual γH2AX, and down-regulated DNA repair proteins Ku70/Ku80.
Conclusions:
- UHRF1 plays a crucial role in promoting radioresistance in ESCC.
- Targeting UHRF1 can enhance radiosensitivity in ESCC cells.
- UHRF1 inhibition impacts cell cycle, apoptosis, and DNA repair, offering a potential therapeutic strategy for overcoming radioresistance in ESCC.
