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TRIM56 Reduces Radiosensitization of Human Glioblastoma by Regulating FOXM1-Mediated DNA Repair

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Abstract

Recurrent glioblastoma is characterized by resistance to radiotherapy or chemotherapy. In this study, we investigated the role of TRIM56 in radiosensitization and its potential underlying molecular mechanism. TRIM56 expression levels were measured in glioblastoma tissues and cell lines by immunohistochemical staining, western blot, and qRT-PCR. MTT assay, colony formation assay, and TUNEL assay were used to investigate the effect of TRIM56 on cell viability, cell proliferation, and cell apoptosis. Co-immunoprecipitation was used to clarify the interaction between TRIM56 and FOXM1. Finally, tumor xenograft experiments were performed to analyze the effect of TRIM56 on tumor growth in vivo. The expression of TRIM56 was significantly increased in glioblastoma tissues and cell lines and its expression was associated with poor prognosis of patients with glioblastoma. Moreover, TRIM56 reduced the radiosensitivity of glioblastoma cells and promoted DNA repairment. Mechanistically, TRIM56 promoted FOXM1 protein level, enhanced the stability of FOXM1 by de-ubiquitination, and promoted DNA damage repair through FOXM1 in glioblastoma cells. TRIM56 could reduce the radiosensitivity of glioblastoma in vivo. TRIM56 may suppress the radiosensitization of human glioblastoma by regulating FOXM1-mediated DNA repair. Targeting the TRIM56 may be an effective method to reverse radiotherapy-resistant in glioblastoma recurrent.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

TRIM:

Tripartite-motif

TRIM56:

Tripartite-motif-containing protein 56

Ub:

Ubiquitin

PCBP1:

Poly r(C) binding protein 1

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Acknowledgements

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Funding

This work was supported by the National Natural Science Foundation of China (31700932), the National Natural Science Foundation of China (81973531), the National Natural Science Foundation of China (82073937), Shenzhen Science and Technology Project (JCYJ20180228175059744), and Shenzhen Key Medical Discipline Construction Fund (SZXK059). Shenzhen Science and Technology Innovation Committee for Basic Research (Grant No. JCYJ20170818144044876).

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Authors and Affiliations

  1. School of Pharmacy and Food Sciences, Zhuhai College of Science and Technology, Zhuhai, 519040, Guangdong Province, China

    Yun Dong

  2. School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Nanshan District, No.1066, Xueyuan Road, Shenzhen City, 518055, Guangdong Province, China

    Yun Dong, Yiping Xiong, Duanyang Zhou, Min Yao, Wenchuan Bi & Jian Zhang

  3. Department of Pharmacy, Shenzhen People’s Hospital, Shenzhen City, 815020, Guangdong Province, China

    Xiao Wang

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  1. Yun Dong
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  4. Min Yao
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Contributions

Yun Dong and Yiping Xiong designed the study and supervised the data collection, Duanyang Zhou analyzed the data and interpreted the data, and Min Yao, Xiao Wang, Wenchuan Bi, and Jian Zhang prepare the manuscript for publication and reviewed the draft of the manuscript. All authors have read and approved the manuscript.

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Correspondence to Wenchuan Bi or Jian Zhang.

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All procedures performed in studies involving human participants were in accordance with the standards upheld by the Ethics Committee of Shenzhen University and with those of the 1964 Helsinki Declaration and its later amendments for ethical research involving human subjects. All animal experiments were approved by the Ethics Committee of Shenzhen University for the use of animals and conducted in accordance with the National Institutes of Health Laboratory Animal Care and Use Guidelines.

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Dong, Y., Xiong, Y., Zhou, D. et al. TRIM56 Reduces Radiosensitization of Human Glioblastoma by Regulating FOXM1-Mediated DNA Repair. Mol Neurobiol 59, 5312–5325 (2022). https://doi.org/10.1007/s12035-022-02898-0

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