Department of Orthopedic Surgery, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai 200233, P.R. China.
Int J Oncol. 2018 Apr;52(4):1277-1284. doi: 10.3892/ijo.2018.4278. Epub 2018 Feb 20.
Sex determining region Y-box protein 3 (SOX3) is involved in embryonic development and tumorigenesis. However, the expression and precise role of SOX3 in osteosarcoma remain unclear. In this study, we reported that SOX3 expression was upregulated in osteosarcoma tissues compared with non-cancerous bone cyst tissues. To elucidate the cellular and molecular function of SOX3, we examined the consequences of SOX3 knockdown in osteosarcoma cells. We found that the downregulation of SOX3 inhibited the proliferation, migration and invasion of osteosarcoma cells. SOX3 downregulation also increased the cell population in the G1 phase and induced cell apoptosis. SOX3 knockdown-mediated cell cycle arrest and cell apoptosis were associated with decreased levels of Cdc25A, cyclin D1, proliferating cell nuclear antigen (PCNA) and Bcl-2, as well as an increased Bax expression. We also found that the downregulation of SOX3 decreased the expression of Snail, Twist and matrix metalloproteinase-9 (MMP-9), and increased E-cadherin expression, resulting in the inhibition of cell migration and invasion. Taken together, our data indicate that SOX3 may serve as an oncogene in osteosarcoma, and SOX3 downregulation may prove to be a novel approach for the inhibition of osteosarcoma progression.
性别决定区 Y 框蛋白 3（SOX3）参与胚胎发育和肿瘤发生。然而，SOX3 在骨肉瘤中的表达和确切作用仍不清楚。在本研究中，我们报道 SOX3 在骨肉瘤组织中的表达高于非癌性骨囊肿组织。为了阐明 SOX3 的细胞和分子功能，我们研究了 SOX3 敲低对骨肉瘤细胞的影响。结果发现，SOX3 的下调抑制了骨肉瘤细胞的增殖、迁移和侵袭。SOX3 下调还增加了 G1 期细胞群体并诱导细胞凋亡。SOX3 下调介导的细胞周期停滞和细胞凋亡与 Cdc25A、细胞周期蛋白 D1、增殖细胞核抗原（PCNA）和 Bcl-2 水平降低以及 Bax 表达增加有关。我们还发现，SOX3 的下调降低了 Snail、Twist 和基质金属蛋白酶 9（MMP-9）的表达，增加了 E-钙黏蛋白的表达，从而抑制了细胞迁移和侵袭。综上所述，我们的数据表明 SOX3 可能在骨肉瘤中作为癌基因发挥作用，SOX3 的下调可能被证明是抑制骨肉瘤进展的一种新方法。
