Zhang Weifei, Yu Fei, Weng Jian, Zheng Yien, Lin Jianjing, Qi Tiantian, Wei Yihao, Wang Deli, Zeng Hui
Department of Bone and Joint Surgery, Peking University Shenzhen Hospital, Shenzhen, China.
National & Local Joint Engineering Research Center of Orthopedic Biomaterials, Peking University Shenzhen Hospital, Shenzhen 518036, China.
Stem Cells Int. 2021 Oct 23;2021:9941733. doi: 10.1155/2021/9941733. eCollection 2021.
SOX12 plays a role in promoting the growth of some tumors; however, its role in osteosarcoma remains unclear. From gene expression omnibus (GEO) and tumor alterations relevant for genomics-driven therapy (TARGET) databases, Kaplan-Meier analyses were conducted to establish relationships between SOX12 expression and osteosarcoma survival and recurrence in osteosarcoma patients. We also performed and assays to determine SOX12 function in osteosarcoma etiology. SOX12 expression was increased in osteosarcoma; high SOX12 expression levels were related to a poor prognosis and a high disease recurrence in patients. Moreover, SOX12 expression in osteosarcoma cell lines was increased, similar to osteosarcoma cancer stem cells. We also observed that SOX12 knockdown inhibited the spheroidization and expression of stemness markers in osteosarcoma cells and tumor formation in nude mice. In addition, SOX12 knockdown inhibited JAGGED1 and HES1 expression. Similarly, JAGGED1 knockdown also inhibited the formation of osteosarcoma cancer stem cells into pellets and reduced the expression of stemness markers and tumor formation capabilities in nude mice. Finally, during SOX12 knockdown, JAGGED1 overexpression rescued osteosarcoma cells from spheroidizing. SOX12 promotes stem cell-like phenotypes and osteosarcoma tumor growth by upregulating JAGGED1.
SOX12在促进某些肿瘤生长中发挥作用；然而，其在骨肉瘤中的作用仍不清楚。从基因表达综合数据库（GEO）和肿瘤基因组学驱动治疗相关改变数据库（TARGET）中，进行了Kaplan-Meier分析，以建立SOX12表达与骨肉瘤患者生存及复发之间的关系。我们还进行了[具体实验名称1]和[具体实验名称2]实验，以确定SOX12在骨肉瘤病因学中的功能。SOX12在骨肉瘤中表达增加；高SOX12表达水平与患者预后不良和疾病高复发率相关。此外，骨肉瘤细胞系中SOX12的表达增加，类似于骨肉瘤癌干细胞。我们还观察到，敲低SOX12可抑制骨肉瘤细胞的球状体形成和干性标志物的表达以及裸鼠体内肿瘤的形成。此外，敲低SOX12可抑制JAGGED1和HES1的表达。同样，敲低JAGGED1也可抑制骨肉瘤癌干细胞形成球状体，并降低干性标志物的表达和裸鼠体内肿瘤形成能力。最后，在敲低SOX12期间，JAGGED1过表达可使骨肉瘤细胞免于球状体形成。SOX12通过上调JAGGED1促进干细胞样表型和骨肉瘤肿瘤生长。
