Department of Spinal Surgery, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, Guangxi, China.
Department of Orthopaedics, Jiangxi Provincial People's Hospital Affiliated to Nanchang University, No. 152 Aiguo Road, Nanchang, 330006, Jiangxi, China.
J Orthop Surg Res. 2020 Jun 18;15(1):226. doi: 10.1186/s13018-020-01681-y.
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.
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.
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.
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.
骨肉瘤是最常见的恶性骨肿瘤之一，全球年发病率约为每百万分之四。骨肉瘤组织中上调基因 4 (URG4) 的表达与骨肉瘤的复发、转移和不良预后密切相关。然而，URG4 在骨肉瘤中的生物学功能和潜在机制尚未阐明。本研究旨在探讨 URG4 在骨肉瘤中的表达及潜在机制。
采用免疫组织化学（IHC）比较骨肉瘤和正常组织中 URG4 的表达水平。PCR 和 Western blot（WB）技术检测 URG4 mRNA 和蛋白水平。采用划痕愈合和 Transwell 分析评估 URG4 对骨肉瘤细胞迁移和侵袭的影响。细胞计数试剂盒-8 检测和集落增殖实验评估沉默 URG4 对细胞增殖抑制的影响。采用流式细胞术检测细胞周期分布，建立异种移植小鼠模型验证 URG4 在体内的功能。
URG4 在骨肉瘤组织和细胞中高表达，其高表达与骨肉瘤患者 Enneking 分期较晚、肿瘤较大、肿瘤转移有关。siRNA 下调 URG4 可抑制骨肉瘤细胞系的增殖和细胞周期进入 S 期。URG4 在体外和体内促进骨肉瘤细胞的增殖和肿瘤发生。WB 验证了 URG4 通过 pGSK3β/β-catenin/cyclinD1 信号通路促进骨肉瘤细胞增殖。
URG4 在骨肉瘤中高表达，通过 GSK3β/β-catenin/cyclin D1 信号通路促进细胞周期进程，可能成为骨肉瘤的一种新的生物标志物和潜在治疗靶点。
