Abstract
Background
Triple-negative breast cancer (TNBC) is characterized by high aggressiveness, heterogeneity, and poor prognosis. Programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, a crucial type of immune checkpoint inhibitor therapy, have been proven to be a promising strategy for the TNBC treatment. Forebrain embryonic zinc finger 2 (FEZF2) is dysregulated in various cancers and participates in the tumor progression. However, its role and mechanism in TNBC remain unknown.
Objectives
To investigate whether FEZF2 is involved in the progression of TNBC via EZH2/PD-L1 axis.
Results
The expression of FEZF2 was downregulated in TNBC. Overexpression of FEZF2 reduced cell viability and enhanced cell apoptosis in both MDA-MB-231 and BT-549 cells. Meanwhile, upregulation of FEZF2 decreased the relative protein expression of EZH2 and PD-L1, which was restored by overexpression of EZH2 in both cells. Moreover, overexpression of PD-L1 neutralized the inhibitory effect of the FEZF2 overexpression on the cell viability in MDA-MB-231 and BT-549 cells. Furthermore, overexpression of FEZF2 reduced the tumor weight and volume, and increased numbers of CD8+ tumor-infiltrating lymphocytes in xenografted mice.
Conclusion
Overexpression of FEZF2 inhibited the proliferation and enhanced the apoptosis of TNBC cells through EZH2/PD-L1 axis, as well as promoted anti-tumor immunity in vivo.
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Data availability
The authors declare that all data supporting the findings of this study are available within the paper and any raw data can be obtained from the corresponding author upon request.
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This work was supported by The Hospital Youth Fund, the First Affiliated Hospital of USTC (Grant no. 2020YJQN021).
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WL and HL designed the study and carried them out; WL, HL, WL, QZ, QZ, and DH supervised the data collection, analyzed the data, interpreted the data; WL and HL prepared the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.
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Wenyu Li declares that he/she has no conflict of interest; Hu Liu declares that he/she has no conflict of interest; Wenjuan Li declares that he/she has no conflict of interest; Qiujun Zhang declares that he/she has no conflict of interest; Qianyu Zhang declares that he/she has no conflict of interest; Dandan Hu declares that he/she has no conflict of interest.
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Ethical approval was obtained from the Laboratory Animals Ethics Committee of the First Affiliated Hospital of USTC (Approval no. 2022-N(A)-120).
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Li, W., Liu, H., Li, W. et al. FEZF2 inhibits the growth of triple-negative breast cancer cells through EZH2/PD-L1 and enhances anti-tumor immunity in vivo. Mol. Cell. Toxicol. 20, 553–562 (2024). https://doi.org/10.1007/s13273-023-00368-9
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DOI: https://doi.org/10.1007/s13273-023-00368-9