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Updated: Nov 14, 2025
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
CTCF-silenced miR-137 contributes to EMT and radioresistance in esophageal squamous cell carcinoma
Shuwen Xu1, Xiaofeng Li2, Longfei Li3
1Department of Head and Neck Surgery, Xuzhou Cancer Hospital, Xuzhou, 221005, Jiangsu, China.
Background:
Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system. MicroRNAs (miRNAs) have been reported to be implicated in cancer development. However, the role of miR-137 has not been fully revealed in ESCC.
Methods:
Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were separately used to examine RNA level and protein level. 5-ethynyl-2'-deoxyuridine (EdU) assay, transwell assays and flow cytometry analyses were conducted to assess biological behaviors of ESCC cells. Additionally, the interaction between genes were analyzed via Chromatin Immunoprecipitation (ChIP) assay, RNA Binding Protein Immunoprecipitation (RIP) assay, RNA pull down assay and luciferase reporter assay.
Results:
MiR-137 was down-regulated in ESCC cells. Upregulation of miR-137 hindered ESCC cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT). Besides, miR-137 enhanced the sensitivity of ESCC cells to irradiation. Moreover, CCCTC-binding factor (CTCF) inactivated miR-137 transcription in ESCC cells. Furthermore, we revealed enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and paxillin (PXN) as the downstream targets of miR-137. In turn, EZH2 was recruited by CTCF and induced methylation in miR-137 promoter.
Conclusion:
CTCF/Suz12/EZH2 complex-silenced miR-137 facilitates ESCC progression and radioresistance by targeting EZH2 and PXN.
Insights
MicroRNA-137 (miR-137) suppresses esophageal squamous cell carcinoma (ESCC) progression and enhances radioresistance. Its silencing by the CTCF/Suz12/EZH2 complex promotes ESCC by targeting EZH2 and PXN.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Esophageal squamous cell carcinoma (ESCC) is a highly aggressive gastrointestinal malignancy.
- MicroRNAs (miRNAs) play critical roles in cancer development, but miR-137's function in ESCC remains unclear.
Purpose of the Study:
- To investigate the role of miR-137 in esophageal squamous cell carcinoma (ESCC).
- To elucidate the regulatory mechanism of miR-137 and its downstream targets in ESCC progression and radioresistance.
Main Methods:
- Quantitative real-time PCR and Western blot for gene and protein expression analysis.
- Cellular assays including EdU, Transwell, and flow cytometry to assess cell behavior.
- ChIP, RIP, RNA pull-down, and luciferase assays to analyze molecular interactions.
Main Results:
- MiR-137 was significantly downregulated in ESCC cells.
- Overexpression of miR-137 inhibited ESCC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while enhancing radiosensitivity.
- CCCTC-binding factor (CTCF) inactivated miR-137 transcription, and the CTCF/Suz12/EZH2 complex mediated miR-137 promoter methylation.
- EZH2 and PXN were identified as direct downstream targets of miR-137.
Conclusions:
- The CTCF/Suz12/EZH2 complex-mediated silencing of miR-137 promotes ESCC progression and radioresistance.
- Targeting EZH2 and PXN by miR-137 is a key mechanism in its tumor-suppressive function.
- Restoring miR-137 levels may represent a therapeutic strategy for ESCC.
