Abstract
Background
Endometrial carcinoma (EC) is the most prevalent gynecological cancer. Transcription factor (TF) regulates a large number of downstream target genes and is a key determinant of all physiological activities, including cell proliferation, differentiation, apoptosis, and cell cycle. The transcription factor E2F1 shows prominent roles in EC. BMI1 is a member of Polycomb suppressor Complex 1 (PRC1) and has been shown to be associated with EC invasiveness. It is currently unclear whether E2F1 can participate in the proliferation, migration, and invasion processes of EC cells by regulating BMI1 transcription.
Objective
We investigated whether E2F1 could participate in the proliferation, migration, and invasion processes of EC cells by regulating BMI1 transcription, in order to further clarify the pathogenesis and etiology of EC, and provide reference for identifying potential therapeutic targets and developing effective prevention and treatment strategies for this disease.
Methods
Human endometrial epithelial cells (hEECs) and human EC cell lines were selected. E2F1 expression was assessed by Western blot. E2F1 was silenced in AN3CA or overexpressed in HEC-1 by transfections, or E2F1 was silenced and BMI1 was overexpressed in AN3CA by cotransfection. Cell proliferation, migration, and invasion were detected by MTT, wound healing, and Transwell assays. The binding sites between E2F1 and BMI1 promoters were predicted through JASPAR website, and the targeted binding was verified by dual-luciferase report and ChIP assays.
Results
E2F1 was up-regulated in human EC cell lines, with its expression highest in AN3CA, and lowest in HEC-1. AN3CA invasion, migration, and proliferation were repressed by E2F1 knockdown, while those of HEC-1 cells were promoted by E2F1 overexpression. E2F1 overexpression increased the activity of wild type BMI1 reporter vector promoter, while this promotion was weakened after mutation of the predicted binding site in the BMI1 promoter. In the precipitated E2F1, BMI1 promoter site level was higher than that of IgG immunoprecipitant. BMI1 silencing suppressed AN3CA cell growth. BMI1 overexpression partially abrogated E2F1 silencing-inhibited EC cell growth.
Conclusion
E2F1 promoted EC cell proliferation, invasion, and migration by promoting the transcription of BMI1.
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Data Availability
All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.
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This work was partially supported by grants from Project of State Key Laboratory of Radiation Medicine and Protection, Soochow University (GZK 1202212).
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YL conceived the ideas. YL, RZ and YW designed the experiments. YL, YW, XS, and YT performed the experiments. YL, JL, YZ and YM analyzed the data. YL wrote the manuscript. YL and RZ supervised the study. All the authors have read and approved the final version for publication.
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Lu, Y., Wei, Y., Shen, X. et al. Mechanism of E2F1 in the proliferation, migration, and invasion of endometrial carcinoma cells via the regulation of BMI1 transcription. Genes Genom 45, 1423–1431 (2023). https://doi.org/10.1007/s13258-023-01416-3
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DOI: https://doi.org/10.1007/s13258-023-01416-3