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Fear stress promotes glioma progression through inhibition of ferroptosis by enhancing FSP1 stability

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Abstract

Purpose

Patients diagnosed with cancer often suffer from emotional stressors, such as anxiety, depression, and fear of death. However, whether fear stress could influence the glioma progression is still unclear.

Methods

Xenograft glioma animal models were established in nude mice. Tumor-bearing mice were subjected to fear stress by living closely with cats and then their depressive behaviors were measured using an open field test. Hematoxylin and eosin staining, the TUNEL staining and immunochemical staining were used to detect the histopathological changes of tumor tissues. Gene expression profiling was used to screen the aberrant gene expression. Methylated RNA immunoprecipitation was used to identify the RNA m6A level. Gene expression was measured by western blot and real-time PCR, respectively.

Results

We found that fear stress promoted glioma tumor progression in mice. Fear stress-induced upregulation of METTL3 and FSP1, increased m6A level of glioma tumor tissues, and inhibited ferroptosis in glioma progression, which were reversed by knockdown of METTL3 and FSP1 in vivo. In addition, we found that when iFSP1 (a ferroptosis inducer by targeting inhibition of FSP1) was introduced to glioma cells, the cells viability of glioma significantly was decreased and ferroptosis was enhanced in glioma cells.

Conclusions

Fear stress-induced upregulation of METTL3 stabilized FSP1 mRNA by m6A modification, leading to tumor progression through inhibition of ferroptosis. Our study provides a new understanding of psychological effects on glioma development, and new insights for glioma therapy.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank all the researchers and study participants for their contributions.

Funding

This work was supported by Education Development Foundation of Henan University (No.: 2019004), Key Scientific and Technological Projects in Henan Province (No. 192102310126).

Author information

Author notes

  1. Chaojie Bu and Sen Hu contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Psychology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, 450003, Henan, People’s Republic of China

    Chaojie Bu

  2. Department of Medical Records, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, 450003, Henan, People’s Republic of China

    Sen Hu

  3. Department of Neurosurgery, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Henan, 450003, Zhengzhou, People’s Republic of China

    Jinliang Yu, Nianxuan Li, Jianjun Gu, Zhiyuan Sheng, Zhaoyue Yan & Xingyao Bu

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  1. Chaojie Bu
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Contributions

SH and JY were responsible for animal and cell experiments, and data analysis. NL, JG, ZS and ZY contributed to animal experiments and partial cell experiments. CB participated in subject design, experimental quality control and paper writing. All of authors read and approved the final manuscript.

Corresponding author

Correspondence to Xingyao Bu.

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The authors declare that they have no conflict of interest.

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The study was approved by Ethical Committee of Zhengzhou University People’s Hospital and conducted in accordance with the ethical standards.

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Bu, C., Hu, S., Yu, J. et al. Fear stress promotes glioma progression through inhibition of ferroptosis by enhancing FSP1 stability. Clin Transl Oncol 25, 1378–1388 (2023). https://doi.org/10.1007/s12094-022-03032-1

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  • DOI: https://doi.org/10.1007/s12094-022-03032-1

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