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TRIM4 Expression Related to Malignant Progression and Cisplatin Resistance in Osteosarcoma

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Abstract

Osteosarcoma (OS) is a high-grade intraosseous malignancy. Twenty to thirty percent of OS patients react poorly to standard therapy with a combination of surgical resection and chemotherapy. It is necessary to find molecules that play an important role in this. This study explored the role of TRIM4 in OS chemotherapy sensitivity and malignant progression. The expression of TRIM4 in OS tissues and cells was examined by RT-qPCR, immunohistochemical staining, and western blot. Specific siRNA was transfected into U2-OS and SAOS2 cells to target TRIM4. Cell biological behavior was examined by CCK-8, Transwell, and flow cytometry experiments. Cisplatin-resistant SAOS2 (SAOS2-Cis-R) cells were established, and the effect of TRIM4 expression on the cisplatin response of SAOS2 cells was tested. Knockdown of TRIM4 significantly inhibited the proliferation, migration, and invasion of U2-OS and SAOS2 cells and induced apoptosis. TRIM4 expression was significantly higher in chemotherapy-resistant OS tissues compared to chemotherapy-sensitive OS tissues. Furthermore, the expression of TRIM4 in SAOS2-Cis-R cells was significantly increased compared to parental SAOS2 cells. Moreover, overexpression of TRIM4 enhanced cisplatin resistance in parental SAOS2 cells, while the downregulation of TRIM4 expression enhanced cisplatin sensitivity of SAOS2-Cis-R cells. High TRIM4 expression might be associated with malignant progression and poor response to chemotherapy response of OS. Targeting TRIM4 may be beneficial for OS treatment or combination therapy.

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Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Joint Surgery, Shandong Second Provincial General Hospital, No.4 Duanxing West Road, Huaiyin District, Jinan, 250022, People’s Republic of China

    Yan Li, Jie Gao, Dong Wang, Zijin Liu & Huawu Zhang

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  1. Yan Li
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  2. Jie Gao
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  3. Dong Wang
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  4. Zijin Liu
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Contributions

Yan Li and Jie Gao carried out the experiments and drafted the manuscript; Dong Wang contributed to the immunohistochemistry experiments; Zijin Liu was involved in the statistical analysis; Huawu Zhang managed the experimental design, reviewed the manuscript, and provided funding support. All authors read and approved the final version of the manuscript.

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Correspondence to Huawu Zhang.

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Ethical Approval

Our study was approved by the Ethics Committee of Shandong Second Provincial General Hospital. All procedures involving people comply with the ethical standards of the institutional and/or national committee for research ethics and the 1964 Helsinki Declaration and its subsequent changes or comparable ethical standards.

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The study was approved by the patient’s written consent and the institutional research ethics committee.

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All other authors have read the manuscript and have agreed to submit it in its current form for consideration for publication in the Applied Biochemistry and Biotechnology.

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The authors declare no competing interests.

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Li, Y., Gao, J., Wang, D. et al. TRIM4 Expression Related to Malignant Progression and Cisplatin Resistance in Osteosarcoma. Appl Biochem Biotechnol 196, 233–244 (2024). https://doi.org/10.1007/s12010-023-04551-5

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