TRIM37 promotes tumor cell proliferation and drug resistance in pediatric osteosarcoma

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.

WITHDRAWN: Tripartite Motif Containing 37 Activates the Wnt/β-catenin Signalling Pathway and Confers Cisplatin Resistance to Ovarian Carcinoma

“…Multiple studies reported that TRIM37 is overexpressed in cancers, including colorectal cancer, pediatric osteosarcoma, pancreatic cancer cells and hepatocellular carcinoma, however, the mechanism of TRIM37 upregulation in cancer remains unknown [33][34][35][36]. Interestingly, we found that TRIM37 exhibited a high ampli cation rate of 21.3% in ovarian cancer according to copy number variation analysis of TCGA datasets (https://www.cureline.com/the-cancer-genome-atlas.html), suggesting that the overexpression of TRIM37 in ovarian cancer is associated with genomic ampli cation.…”

TROP2 promotes cell proliferation and migration in osteosarcoma through PI3K/AKT signaling

“…The overall survival rate of patients with OS is reported to be 60-80% (2)(3)(4). However, despite the advances in multiagent chemotherapy and surgical technique, the survival rate of patients with locally advanced or metastatic tumors at diagnosis is still very low (<20%) (5)(6)(7)(8)(9). Thus, there is urgent need to reveal detailed signal pathways involved in OS pathogenesis and the molecular mechanism of its metastasis, which may provide novel therapeutic targets for the clinical management of OS.…”

Targeting Molecular Mechanisms Underlying Treatment Efficacy and Resistance in Osteosarcoma: A Review of Current and Future Strategies

“…Upregulation of TRIM37 in vitro induced drug resistance, whereas TRIM37 knockdown restored chemosensitivity. The TRIM37-induced chemoresistance was found to be partially dependent on the activation of the Wnt/β-catenin signalling pathway [399]. These findings implicate the Wnt/β-catenin signalling pathway in chemoresistance in osteosarcoma and suggest that TRIM37 could be used as a target to supress activity of this pathway and increase drug sensitivity.…”