Abstract
Background
Nasopharyngeal carcinoma (NPC) is the most common head and neck tumor in China. Forkhead box (FOX) proteins have 19 subfamilies, which can maintain cell metabolism, regulate cell cycle and cell growth, etc. FOXK1 is a member of the FOX family, and studies have found that FOXK1 is closely related to tumors.
Objective
This experiment aims to study the effects of FOXK1 interference on proliferation, apoptosis, invasion, epithelial-mesenchymal transition (EMT), and radiosensitivity, by regulating the Janus kinas/signal translator and activator of the transfer 3 (JAK/STAT3) pathway.
Methods
The expression of FOXK1 was detected via immunohistochemistry using clinical nasopharyngeal carcinoma tissues and adjacent tissues. The relationship between FOXK1 expression and tumor stage was subsequently evaluated. The colony formation rate was calculated through the colony formation experiment. Cell apoptosis and cell cycle distribution were detected using flow cytometry, while cell invasion was detected using the Transwell method. The number of cells in the nucleus of each group after 30 min, 4 h, and 24 h of radiotherapy with the 2 Gy dose was counted using immunofluorescence under γ-H2AX focal points of a laser confocal microscope.
Results
FOXK1 is clearly expressed in the patients’ cancer tissues. The expression of FOXK1 was significantly correlated with the patient’s sex. FOXK1 interference or Peficitinib can upregulate the apoptosis rate of 5-8 F and CNE-2 cells; increase the G2 phase of cells; and inhibit the invasion, migration, and EMT of cells. At the same time, FOXK1 interference can downregulate the protein expression of p-JAK1, p-JAK2, and p-STAT3 in cells. Interference from FOXK1 or Peficitinib alone can reduce the rate of cell colony formation under different radiation doses, and enhance the green fluorescence intensity of γ-H2AX in the nucleus after 4 and 24 h of the 2 Gy dose of radiotherapy. These results are optimal when FOXK1 interference and Peficitinib are used together.
Conclusion
FOXK1 interference in NPC cells can regulate EMT through the JAK/STAT3 signal pathway, enhance the radiosensitivity of cells, and thus inhibit tumor cell progression.
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Data Availability
The data used to support the findings of this study are available from the corresponding author upon request.
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This project was supported by National Natural Science Foundation of China (81903137).
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Liqun Duan, Jinlong Huang, Yong Zhang, Guoliang Pi, Xiaofang Ying, Fanyu Zeng, DeshengHu and Jia Ma declare that they have no conflict of interest.
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Liqun Duan and Jinlong Huang contributed equally to this study.
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Duan, L., Huang, J., Zhang, Y. et al. FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway. Genes Genom 45, 749–761 (2023). https://doi.org/10.1007/s13258-023-01380-y
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DOI: https://doi.org/10.1007/s13258-023-01380-y