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LTF Induces Radioresistance by Promoting Autophagy and Forms an AMPK/SP2/NEAT1/miR-214-5p Feedback Loop in Lung Squamous Cell Carcinoma  期刊论文  

  • 编号:
    6046619AEADF7DA44242FB4DBA68CE25
  • 作者:
    Wen, Junmiao[1,2,3] Zheng, Wang[4,5] Zeng, Liang[4] Wang, Boyan[1,2,3] Chen, Donglai[6] Chen, Yongbing[7] Lu, Xueguan[1,2] Shao, Chunlin[4,9] Chen, Jiayan[1,2,3,8] Fan, Min[1,2,3,8]
  • 语种:
    英文
  • 期刊:
    INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES ISSN:1449-2288 2023 年 19 卷 5 期 (1509 - 1527)
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  • 摘要:

    Radiotherapy is the most predominant treatment strategy for lung squamous cell carcinoma (LUSC) patients, but radioresistance is the major obstacle to therapy effectiveness. The mechanisms and regulators of LUSC radioresistance remain unclear. Here, lactotransferrin (LTF) is found to be significantly upregulated in radioresistant LUSC cell lines (H226R and H1703R) and clinical samples and promotes radioresistance of LUSC both in vitro and in vivo. Comprehensive enrichment analyses suggested that LTF potentially modulates autophagy in LUSC. Interestingly, the level of autophagy was raised in the radioresistant cells, and suppression of autophagy sensitized LUSC to irradiation. Functional experiments showed that LTF deficiency inhibits cellular autophagy through the AMPK pathway, ultimately leading to radiosensitization. Mechanistically, LTF can directly interact with AMPK to facilitate its phosphorylation and activate autophagy signaling. Moreover, NEAT1 functions as a ceRNA that targets miR-214-5p resulting in an increased LTF expression. Intriguingly, SP2, a transcription factor regulated by AMPK, induced NEAT1 expression by directly binding to its promoter region and thus forming a LTF/AMPK/SP2/NEAT1/miR-214-5p feedback loop. Our work reveals for the first time that LTF induces radioresistance by promoting autophagy and enhancing its self-expression via forming a positive feedback loop, suggesting that LTF is an appealing radiosensitization target for treating LUSC.

  • 推荐引用方式
    GB/T 7714:
    Wen Junmiao,Zheng Wang,Zeng Liang, et al. LTF Induces Radioresistance by Promoting Autophagy and Forms an AMPK/SP2/NEAT1/miR-214-5p Feedback Loop in Lung Squamous Cell Carcinoma [J].INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2023,19(5):1509-1527.
  • APA:
    Wen Junmiao,Zheng Wang,Zeng Liang,Wang Boyan,&Fan Min.(2023).LTF Induces Radioresistance by Promoting Autophagy and Forms an AMPK/SP2/NEAT1/miR-214-5p Feedback Loop in Lung Squamous Cell Carcinoma .INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,19(5):1509-1527.
  • MLA:
    Wen Junmiao, et al. "LTF Induces Radioresistance by Promoting Autophagy and Forms an AMPK/SP2/NEAT1/miR-214-5p Feedback Loop in Lung Squamous Cell Carcinoma" .INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 19,5(2023):1509-1527.
  • 入库时间:
    2025/2/19 22:45:58
  • 更新时间:
    2025/2/21 12:42:40
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