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Published on: January 16, 2026
TRAF6 regulates proliferation, apoptosis, and invasion of osteosarcoma cell
Qingbing Meng1, Minqian Zheng, Hongbing Liu
1Orthopedics Department, Yancheng City No. 1 People's Hospital, 16 Yue-He Road, Yancheng, Jiangsu 224005, People's Republic of China. ycmengqingbing@163.com
Abstract:
TRAF6, a unique tumor necrosis factor receptor-associated factor (TRAF) family member, possesses a unique receptor-binding specificity that results in its crucial role as the signaling mediator for TNF receptor superfamily and interleukin-1 receptor/Toll-like receptor superfamily. TRAF6 plays an important role in tumorigenesis, invasion and metastasis. This study aimed to explore the expression of TRAF6 in osteosarcoma tissues and its correlation to the clinical pathology of osteosarcoma and to discuss the relationship between TRAF6 expression and osteosarcoma invasion. These data will provide the experimental base for the biological treatment of osteosarcoma in the future. Using RT-PCR and Western blot, the results showed that the expression rate of TRAF6 mRNA in osteosarcoma tissues was significantly higher than that in normal bone tissue (p < 0.05), that the expression rate of TRAF6 mRNA in the carcinoma tissues from patients with lung metastasis was significantly higher than that from patients without lung metastasis (p < 0.05), and that the expression rate of TRAF6 mRNA also increased with increasing Enneking stage (p < 0.05). However, the mRNA expression of TRAF6 in osteosarcoma was independent of the patient's gender, age, and tumor size (p > 0.05). The TRAF6 protein displayed an up-regulation in osteosarcoma tissues compared to normal bone tissue (p < 0.05), displayed an up-regulation in osteosarcoma tissues from patients with lung metastasis compared to from patients without lung metastasis (p < 0.05), and displayed a gradual increase with increasing Enneking stage (p < 0.05). By the technique of RNA interference, the expression of TRAF6 in the human osteosarcoma MG-63 cell line was down-regulated, and the invasive ability of MG-63 cells was examined. The results showed that TRAF6 protein expression was significantly decreased in the MG-63 cells from TRAF6 siRNA-transfected group (p < 0.05), and the proliferation ability of MG-63 cells and the number of MG-63 cells that passed through the Transwell chamber were significantly lower than that in the non-transfected control group as well as the transfected control group (p < 0.05). In addition, the percentage of MG-63 cells undergoing apoptosis was significantly higher in the TRAF6 siRNA-transfected group compared with the non-transfected control group as well as the transfected control group (p < 0.05). The expression of p-p65, cyclin D1, MMP-9 was down-regulated in the MG-63 cells from TRAF6 siRNA-transfected group. The expression of caspase 3 was up-regulated in the MG-63 cells from TRAF6 siRNA-transfected group compared to the non-transfected control group as well as the transfected control group (p < 0.05). To make a long story short, the overexpression of TRAF6 in osteosarcoma might be related to the tumorigenesis, invasion of osteosarcoma.
Insights
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is overexpressed in osteosarcoma, correlating with tumor progression and metastasis. Reducing TRAF6 expression inhibits osteosarcoma cell invasion and proliferation, suggesting its role in tumorigenesis.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- TRAF6 is a key signaling mediator for TNF and IL-1 receptor superfamilies.
- TRAF6 is implicated in tumorigenesis, invasion, and metastasis.
Purpose of the Study:
- To investigate TRAF6 expression in osteosarcoma tissues.
- To correlate TRAF6 expression with clinical pathology and invasion.
- To explore TRAF6's role in osteosarcoma cell behavior.
Main Methods:
- RT-PCR and Western blot to assess TRAF6 mRNA and protein expression.
- RNA interference (siRNA) to down-regulate TRAF6 in MG-63 cells.
- Transwell assays to evaluate cell invasion and proliferation.
- Apoptosis assays to measure programmed cell death.
Main Results:
- TRAF6 mRNA and protein were significantly upregulated in osteosarcoma tissues, especially with lung metastasis and higher Enneking stage.
- Down-regulation of TRAF6 in MG-63 cells reduced proliferation and invasion, and increased apoptosis.
- TRAF6 knockdown decreased p-p65, cyclin D1, and MMP-9, while increasing caspase 3 expression.
Conclusions:
- TRAF6 overexpression is associated with osteosarcoma tumorigenesis and invasion.
- TRAF6 plays a critical role in regulating osteosarcoma cell proliferation, invasion, and apoptosis.
- TRAF6 may serve as a potential therapeutic target for osteosarcoma.
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