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Updated: Feb 21, 2026

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Sirtuin 7 plays an oncogenic role in human osteosarcoma via downregulating CDC4 expression
Wang Wei1,2, Zhang Xiao Jing1,2, Zheng Ke1,2
1Department of Bone and Soft-Tissue Tumor Surgery, Cancer Hospital of China Medical UniversityShenyang 110042, Liaoning Province, PR China.
Abstract:
It is still a controversy whether the role of Sirtuin 7 (SIRT7) is an oncogene or a tumor suppressor gene in cancer as SIRT7 may have different functions in different types of cancer. Particularly, the specific roles of SIRT7 in the progression of osteosarcoma remain undiscovered. The main aim of this study is to identify the expression of SIRT7 in osteosarcoma and explore the biological functions of SIRT7 in regulating cellular processes of osteosarcoma cells. Here, we show that SIRT7 expression was significantly higher in osteosarcoma tissues and osteosarcoma cell lines than in non-tumor tissues and an immortalized normal cell line, respectively. Moreover, elevated SIRT7 levels in clinical samples indicate a poor prognosis of osteosarcoma patients. SIRT7 knockdown reduces proliferation, migration, invasion, tumor formation, and metastasis of osteosarcoma cells, while SIRT7 overexpression has the opposite effects. Mechanistically, SIRT7 down regulates H3K18ac expression and decreases H3K18ac binding to the promoter region of CDC4, leading to the inhibition of CDC4 transcription. Furthermore, the silencing of CDC4 partially rescued SIRT7 knockdown-mediated inhibitory effects on proliferation, migration, and invasion of osteosarcoma cells. In summary, our results show that SIRT7 promotes proliferation, migration, and invasion of osteosarcoma cells through targeting CDC4, suggesting a potential therapeutic target for SIRT7 based therapy for osteosarcoma.
Insights
Sirtuin 7 (SIRT7) promotes osteosarcoma progression by increasing cell proliferation, migration, and invasion. Targeting SIRT7 could offer a new therapeutic strategy for osteosarcoma patients.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- The role of Sirtuin 7 (SIRT7) in cancer remains controversial, with varying functions across different cancer types.
- The specific involvement of SIRT7 in osteosarcoma progression is not yet understood.
Purpose of the Study:
- To investigate SIRT7 expression levels in osteosarcoma.
- To explore the biological functions of SIRT7 in osteosarcoma cell processes.
- To elucidate the underlying molecular mechanisms of SIRT7 action in osteosarcoma.
Main Methods:
- Quantitative analysis of SIRT7 expression in osteosarcoma tissues and cell lines.
- Functional assays including proliferation, migration, invasion, tumor formation, and metastasis assays.
- Mechanistic studies involving histone modification (H3K18ac) and gene transcription (CDC4).
Main Results:
- SIRT7 expression is significantly elevated in osteosarcoma tissues and cell lines compared to non-tumor controls.
- Higher SIRT7 levels correlate with a poorer prognosis in osteosarcoma patients.
- SIRT7 knockdown inhibits osteosarcoma cell proliferation, migration, invasion, tumor formation, and metastasis.
- SIRT7 promotes osteosarcoma progression by downregulating H3K18ac and inhibiting CDC4 transcription.
- Silencing CDC4 partially reverses the inhibitory effects of SIRT7 knockdown.
Conclusions:
- SIRT7 acts as an oncoprotein in osteosarcoma, promoting tumor cell proliferation, migration, and invasion.
- SIRT7 exerts its oncogenic function by targeting CDC4 transcription via H3K18ac modification.
- SIRT7 represents a potential therapeutic target for osteosarcoma treatment.
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