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Published on: May 3, 2021
URG4 mediates cell proliferation and cell cycle in osteosarcoma via GSK3β/β-catenin/cyclin D1 signaling pathway
Yayun Liu1,2, Yizhe Xi1, Gang Chen2
1Department of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China.
Background:
Osteosarcoma is one of the most common malignant bone tumors with the annual global incidence of approximately four per million. Upregulated gene 4 (URG4) expression in the osteosarcoma tissue is closely associated with recurrence, metastasis, and poor prognosis of osteosarcoma. However, the biological function and underlying mechanisms of URG4 in osteosarcoma have not been elucidated. This study aimed to explore the expression and underlying mechanism of URG4 in osteosarcoma.
Methods:
The expression level of URG4 in osteosarcoma and normal tissues was compared using immunohistochemistry (IHC). PCR and western blotting (WB) techniques are used to detect URG4 mRNA and protein levels. Wound healing and Transwell analysis to assess the effect of URG4 on osteosarcoma cell migration and invasion. Cell Counting Kit-8 assay and colony proliferation assay were performed to evaluate the effects of silencing URG4 on the inhibition of cell proliferation. The cell cycle distribution was detected by flow cytometry, and a xenograft mouse model was used to verify the function of URG4 in vivo.
Results:
URG4 was found to be highly expressed in osteosarcoma tissues and cells, and its high expression was correlated with advanced Enneking stage, large tumor size, and tumor metastasis in osteosarcoma patients. The proliferation in osteosarcoma cell lines and cell cycle in the S phase was suppressed when siRNA was used to downregulate URG4. URG4 promoted cell proliferation and tumorigenesis in vitro and in vivo. WB verified that URG4 promotes cell proliferation in osteosarcoma via pGSK3β/β-catenin/cyclinD1 signaling.
Conclusion:
URG4, which is high-expressed in osteosarcoma, promotes cell cycle progression via GSK3β/β-catenin/cyclin D1 signaling pathway and may be a novel biomarker and potential target for the treatment of osteosarcoma.
Insights
Upregulated gene 4 (URG4) promotes osteosarcoma progression by enhancing cell cycle and proliferation via the GSK3β/β-catenin/cyclin D1 pathway, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a common malignant bone tumor with poor prognosis.
- Upregulated gene 4 (URG4) expression correlates with osteosarcoma recurrence, metastasis, and poor outcomes.
- The precise role and mechanisms of URG4 in osteosarcoma remain unclear.
Purpose of the Study:
- To investigate the expression patterns of URG4 in osteosarcoma.
- To elucidate the functional role of URG4 in osteosarcoma progression.
- To explore the underlying molecular mechanisms of URG4 action in osteosarcoma.
Main Methods:
- Immunohistochemistry (IHC), PCR, and Western blotting (WB) to assess URG4 expression.
- In vitro assays (wound healing, Transwell, CCK-8, colony formation) to evaluate URG4's effect on cell migration, invasion, and proliferation.
- Flow cytometry for cell cycle analysis and xenograft models for in vivo validation.
Main Results:
- URG4 is highly expressed in osteosarcoma tissues and cells, linked to advanced stage and metastasis.
- Downregulation of URG4 using siRNA suppressed osteosarcoma cell proliferation and cell cycle progression.
- URG4 promotes osteosarcoma cell proliferation and tumorigenesis in vitro and in vivo via the pGSK3β/β-catenin/cyclin D1 signaling pathway.
Conclusions:
- High URG4 expression in osteosarcoma drives cell cycle progression through the GSK3β/β-catenin/cyclin D1 signaling pathway.
- URG4 represents a potential novel biomarker and therapeutic target for osteosarcoma treatment.
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