Rui Jiang, Department of Orthopedic Surgery, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130033, PR China.
Zhong-li Gao, Department of Orthopedic Surgery, China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130033, PR China.
Pak J Med Sci. 2013 Jul;29(4):997-1002. doi: 10.12669/pjms.294.3498.
To investigate the role of Zinc finger X-chromosomal protein (ZFX) in oncogenesis of Osteosarcoma tumor.
Here, we first conducted an expression analysis of ZFX in Osteosarcoma cell lines. Then, we constructed ZFX-specific small interfering RNA (siRNA)-lentiviral vector that is capable of effectively inhibiting the expression of ZFX gene in human Osteosarcoma Saos-2 cells, and investigated systemically the impacts of ZFX silence on the growth and invasive ability of the cancer cells in vitro. Furthermore, we determined the effects of ZFX knockdown on the cell cycle distribution and apoptosis of Saos-2 cells.
We found that ZFX inhibition resulted in significantly impaired proliferation and colony formation as well as mitigated invasiveness of Saos-2 cells. Importantly, si-ZFX infected cells exhibited a greater portion of cells at G1 phase, but a minor portion of S and G2/M phase cells. Moreover, a greater portion of sub-G1 apoptotic cells was observed in si-ZFX infected cells.
These results strongly suggest that ZFX is a novel proliferation regulator that promotes growth of Osteosarcoma cells, and downregulation of ZFX expression induces growth suppression of Saos-2 cells via arrested G0/G1 phase cell cycle and apoptosis pathways, thereby indicating that ZFX may serve as a new molecular target for Osteosarcoma tumor therapy.
研究锌指 X 染色体蛋白(ZFX)在骨肉瘤肿瘤发生中的作用。
我们首先对骨肉瘤细胞系中的 ZFX 表达进行了分析。然后,构建了能够有效抑制人骨肉瘤 Saos-2 细胞中 ZFX 基因表达的 ZFX 特异性小干扰 RNA(siRNA)-慢病毒载体,并系统研究了 ZFX 沉默对体外癌细胞生长和侵袭能力的影响。此外,我们还确定了 ZFX 敲低对 Saos-2 细胞细胞周期分布和凋亡的影响。
我们发现 ZFX 抑制导致 Saos-2 细胞的增殖和集落形成明显受损,侵袭性降低。重要的是,感染 si-ZFX 的细胞中 G1 期细胞比例增加,而 S 和 G2/M 期细胞比例减少。此外,在感染 si-ZFX 的细胞中观察到更多的亚 G1 凋亡细胞。
这些结果强烈表明,ZFX 是一种新型的增殖调节剂,促进骨肉瘤细胞的生长,下调 ZFX 表达通过 G0/G1 期细胞周期和凋亡途径抑制 Saos-2 细胞的生长,表明 ZFX 可能成为骨肉瘤肿瘤治疗的新分子靶点。