Abstract
Background
Many patients with esophageal squamous cell carcinoma (ESCC) are inoperable due to old age or advanced stage; thus, radio- and chemotherapy are considered the standard treatments for these patients. However, due to the radiation resistance of tumor cells that may arise during radiotherapy, results are still not satisfactory. The authors’ previous studies found that microRNA can affect radiosensitivity, and further microRNA research was conducted to improve the radiosensitivity of ESCC.
Methods
Cells were treated with silent miR-29b (si-miR-29b). Thereafter,proliferation, colony formation, cell cycle, and apoptosis were determined. The luciferase reporting assay was used to confirm the direct interaction between miR-29b and BTG2. Serum samples and clinical follow-up data of 75 elderly or advanced ESCC patients who could not tolerate surgery were collected.
Results
The expression level of miR-29 in ESCC serum was closely correlated to radiosensitivity (χ2 =8.36, p < 0.05) and correlated with overall survival (OS; hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.24–0.90). Function assays demonstrated that the number of cell clones increased after radiometry radiation, and the cell cycle was blocked in the G0/G1 phase (from 37.2 to 56.9%) in the si-miR-29b transfection group. Expression of BTG2 was upregulated and expression of cyclin D1 was downregulated (p < 0.05). Transfection of si-BTG2 can reverse this result and restore the expression level of cyclin D1 (p < 0.05). The target gene BTG2 of miR-29b was predicted using a bioinformatics tool and confirmed by dual-luciferase reporter assay.
Conclusion
Silencing of miR-29b in ESCC cells can increase expression of BTG2 and decrease the level of intracellular cyclin D1, resulting in cell cycle arrest and accumulation in the G0/G1 phase. Because G0/G1-phase cells are insensitive to radiotherapy, the sensitivity of radiotherapy is reduced.
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Acknowledgements
Thanks to my mentors for their guidance. Thanks to all the patients who participated in this study and the medical staff of the Fourth Hospital of Hebei Medical University for collecting blood from the patients.
Funding
This study was supported by grants from the National Natural Scientific Foundation of China (81871922).
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D. Guo, J. Jin, J. Liu, X. Dong, D. Li, and Y. He declare that they have no competing interests.
Ethical standards
All procedures performed in studies involving human participants or on human tissue were in accordance with the ethical standards of the institutional (Human Ethics Committee of the Fourth Hospital of Hebei Medical University) and/or national research committee and with the 1975 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants included in the study.
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Guo, D., Jin, J., Liu, J. et al. MicroRNA-29b regulates the radiosensitivity of esophageal squamous cell carcinoma by regulating the BTG2-mediated cell cycle. Strahlenther Onkol 197, 829–835 (2021). https://doi.org/10.1007/s00066-021-01790-5
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DOI: https://doi.org/10.1007/s00066-021-01790-5