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LITAF Enhances Radiosensitivity of Human Glioma Cells via the FoxO1 Pathway

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Abstract

Lipopolysaccharide-induced tumor necrosis factor alpha factor (LITAF), also called p53-induced gene 7 (PIG7), was identified as a transcription factor that activates transcription of proinflammatory cytokines in macrophages in response to lipopolysaccharide (LPS). Previous studies have identified LITAF as a potential tumor suppressor in several neoplasms, including prostate cancer, B-NHL, acute myeloid leukemia, and pancreatic cancer. However, the expression and function of LITAF in human glioma remain unexplained. The present study aimed to analyze the regulation of LITAF in gliomas. Data from The Cancer Genome Atlas (TCGA) database revealed that LITAF mRNA expression in glioma tissues was higher than that in normal brain tissues, and lower LITAF expression in gliomas showed a good prognosis in patients who received radiotherapy, by Kaplan–Meier analysis. In our collected specimens, however, LITAF showed low expression in glioma tissues compared to that in the normal brain tissue. Proliferation and apoptosis of glioma cells were not affected by knockdown or overexpression of LITAF in glioma U251, U373, and U87 cells, but LITAF was able to enhance the radiosensitivity of glioma cells. Furthermore, we found that LITAF enhanced radiosensitivity via FoxO1 and its specific downstream targets BIM, TRAIL, and FASLG. Taken together, our present results demonstrate that LITAF expression is decreased in glioma tissues and might enhance radiosensitivity of glioma cells via upregulation of the FoxO1 pathway.

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Funding

This study was funded by the National Natural Science Foundation of China (No. 81372408).

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Authors and Affiliations

  1. Cancer Research Institute of PLA, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    Changlin Huang, Diangang Chen, Hongfan Zhu & Guanghui Li

  2. Neurosurgery, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China

    Shengqing Lv

  3. Pathology, Southwest Hospital, Army Medical University, Chongqing, 400037, China

    Qingrui Li

Authors
  1. Changlin Huang
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  2. Diangang Chen
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  3. Hongfan Zhu
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  4. Shengqing Lv
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  5. Qingrui Li
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  6. Guanghui Li
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Contributions

CH, DC, and HZ performed the experiments and analyzed the data. SL and QL provided the human specimen. CH and GL wrote the paper. DC and GL designed the research.

Corresponding author

Correspondence to Guanghui Li.

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The authors declare that they have no conflict of interest for this manuscript.

Ethics Approval

All experimental protocols were approved by the Ethics Committee of The Xinqiao Hospital, Chongqing 40037, China (No. AF/SC-08/1.0). All procedures performed in studies involving human specimen were in accordance with the ethical standards.

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Huang, C., Chen, D., Zhu, H. et al. LITAF Enhances Radiosensitivity of Human Glioma Cells via the FoxO1 Pathway. Cell Mol Neurobiol 39, 871–882 (2019). https://doi.org/10.1007/s10571-019-00686-4

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  • DOI: https://doi.org/10.1007/s10571-019-00686-4

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