Yan Guangning, Lv Yangfan, Lai Xuwen, Li Zhenlian, Ye Danli, Wang Wei, Qian Yunfeng, Yu Haojie, Wang Zhuocai
Department of Pathology, General Hospital of Southern Theater Command, Guangzhou, People's Republic of China.
Department of Pathology, The Second affiliated hospital, Army Medical University, Chongqing, People's Republic of China.
Pol J Pathol. 2022;73(4):343-351. doi: 10.5114/pjp.2022.125534.
Osteosarcoma (OS) is the most common malignant bone tumour; however, the underlying mechanisms are mainly unknown. Enhancer of zeste homologue 2 (EZH2) and NOTCH pathway are important molecular signals related to carcinogenesis and tumour progression, but they are not fully understand in OS. Enhancer of zeste homologue 2, Notch3, HES1, and Nanog were detected on OS samples and statistically analysed. Expressions of these genes were investigate, and stem-like phenotype was verified in OS cells. This study found that higher EZH2 expression, Notch3 pathway, or Nanog were associated with tumour relapse and metastasis and a significantly shorter survival time. Moreover, the Notch3 pathway was activated in osteosarcoma stem cells. Enhancer of zeste homologue 2 overexpression could activate the Notch3 pathway and increase HES1 expression, leading to upregulated stem cell-related gene expression and self-renewal of OS cells. Our study demonstrates that EZH2, Notch3, and Nanog are important prognostic factors. Enhancer of zeste homologue 2 could maintain the self-renewal of OS cells, where the Notch3 pathway activation may be involved.
骨肉瘤（OS）是最常见的恶性骨肿瘤；然而，其潜在机制主要尚不清楚。zeste同源物2增强子（EZH2）和NOTCH信号通路是与肿瘤发生和进展相关的重要分子信号，但在骨肉瘤中对它们的了解还不完全。在骨肉瘤样本中检测了zeste同源物2增强子、Notch3、HES1和Nanog，并进行了统计学分析。研究了这些基因的表达情况，并在骨肉瘤细胞中验证了干细胞样表型。本研究发现，较高的EZH2表达、Notch3信号通路或Nanog与肿瘤复发和转移以及显著缩短的生存时间相关。此外，Notch3信号通路在骨肉瘤干细胞中被激活。zeste同源物2增强子过表达可激活Notch3信号通路并增加HES1表达，导致骨肉瘤细胞中干细胞相关基因表达上调和自我更新。我们的研究表明，EZH2、Notch3和Nanog是重要的预后因素。zeste同源物2增强子可维持骨肉瘤细胞的自我更新，其中可能涉及Notch3信号通路的激活。
