FOXK1 regulates epithelial-mesenchymal transition and radiation sensitivity in nasopharyngeal carcinoma via the JAK/STAT3 signaling pathway

Duan Liqun; Huang Jinlong; Zhang Yong; Pi Guoliang; Ying Xiaofang; Zeng Fanyu; Hu Desheng; Ma Jia

doi:10.1007/s13258-023-01380-y

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저자정보: Duan Liqun (Huazhong University of Science and Technology China) Huang Jinlong (People’s Hospital of Dongxihu District China) Zhang Yong (Huazhong University of Science and Technology China) Pi Guoliang (Huazhong University of Science and Technology China) Ying Xiaofang (Huazhong University of Science and Technology China) Zeng Fanyu (Huazhong University of Science and Technology China) Hu Desheng (Huazhong University of Science and Technology China) Ma Jia (Huazhong University of Science and Technology China)

저널정보: 한국유전학회 Genes & Genomics Genes & Genomics Vol.45 No.6

발행연도: 2023.6

수록면: 749 - 761 (13page)

DOI: 10.1007/s13258-023-01380-y

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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.

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.

#Nasopharyngeal carcinoma · FOXK1 · Radiosensitivity · JAK/STAT3 signal pathway · EMT

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Duan Liqun

소속기관 Huazhong University of Science and Technology China

주요연구분야 자연과학 > 생물학

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Huang Jinlong

소속기관 People’s Hospital of Dongxihu District China

주요연구분야 자연과학 > 생물학

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Zhang Yong

소속기관 Huazhong University of Science and Technology China

주요연구분야 자연과학 > 생물학

논문수 1 이용수 1

Pi Guoliang

소속기관 Huazhong University of Science and Technology China

주요연구분야 자연과학 > 생물학

논문수 1 이용수 1

Ying Xiaofang

소속기관 Huazhong University of Science and Technology China

주요연구분야 자연과학 > 생물학

논문수 1 이용수 1

Zeng Fanyu

소속기관 Huazhong University of Science and Technology China

주요연구분야 자연과학 > 생물학

논문수 1 이용수 1

Hu Desheng

소속기관 Huazhong University of Science and Technology China

주요연구분야 자연과학 > 생물학

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Ma Jia

소속기관 Huazhong University of Science and Technology China

주요연구분야 자연과학 > 생물학

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