TRIM37 promotes tumor cell proliferation and drug resistance in pediatric osteosarcoma

Tao,Yanling; Xin,Meiyun; Cheng,Huanchen; Huang,Zongxuan; Hu,Tiantian; Zhang,Teng; Wang,Jianlong

doi:10.3892/ol.2017.7059

TRIM37 promotes tumor cell proliferation and drug resistance in pediatric osteosarcoma

Authors:
- Yanling Tao
- Meiyun Xin
- Huanchen Cheng
- Zongxuan Huang
- Tiantian Hu
- Teng Zhang
- Jianlong Wang
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Affiliations: Department of Pediatrics, Jining Medical University Affiliated Hospital, Jining, Shandong 272000, P.R. China, Harbin Research Institute of Hematology and Oncology, Harbin, Heilongjiang 150001, P.R. China, Department of Pediatrics, Jining First People's Hospital, Jining, Shandong 272000, P.R. China
Published online on: September 26, 2017 https://doi.org/10.3892/ol.2017.7059
Pages: 6365-6372
Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Osteosarcoma (OS) is among the most frequently occurring bone tumors, particularly in children. Clinical treatment of OS is limited due to several factors including resistance to chemotherapy drugs and metastasis, and the underlying molecular mechanisms remain unclear. In the present study, tripartite motif containing 37 (TRIM37) expression levels were upregulated in tumor samples and associated with the development of drug resistance in OS. Furthermore, chemotherapy drug treatment (doxorubicin, cisplatin and methotrexate) induced TRIM37 expression in OS cells in vitro. TRIM37 mRNA and protein were upregulated in 41 pediatric osteosarcoma clinical specimens. To further elucidate the effect of TRIM37, gain and loss‑of‑function analysis was performed. Overexpression of TRIM37 induced cell proliferation and drug resistance ability of OS cells, whilst TRIM37 knockdown suppressed cell growth rate and restored chemosensitivity. TRIM37‑regulated genes were subsequently analyzed by expression microarray and gene set enrichment analysis. Using the Wnt/β‑catenin inhibitor XAV‑939, the present study demonstrated that TRIM37‑induced chemoresistance is partially dependent on the activation of the Wnt/β‑catenin signaling pathway. Collectively, the results of the present study suggest that TRIM37 may have a key role in the development of OS and in the ability for the cells to acquire drug resistance, thus it may be a novel target for the treatment of OS.

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