Department of Orthopedics, Quanzhou Hospital of Fujian Medical University, Quanzhou, Fujian, 362000, PR China.
Department of Orthopaedics, Hospital of Zhengzhou University, Zhengzhou, 450052, PR China.
Biochem Biophys Res Commun. 2019 Mar 19;510(4):525-529. doi: 10.1016/j.bbrc.2019.01.114. Epub 2019 Feb 6.
Osteosarcoma (OS) is an invasive cancer in the skeletal system. The molecular mechanism of its etiology and pathogenesis are still not clear, so the effective treatment strategy of OS needs further research. First, we analyzed the expression level and prognostic ability of the RNA helicase DDX10 in OS patients based on the data obtained from GEO database. Next, we used CCK8 to test OS cell viability. Besides, we used wound-healing assay and transwell migration assay to detect cell migration of OS MG63 cell line. And the cell invasion was tested by transwell invasion assay. Moreover, we used QRT-PCR and western blot to analyze the mRNA and protein expression levels. We found that DDX10 was significantly over-expressed in OS patients and elevated level of DDX10 was associated with a poor prognosis. Silencing of DDX10 inhibited proliferation, invasion and migration of MG63 cells in vitro. Down-regulation of DDX10 inhibited MAPK signaling pathway. The expression of p-MEK and p-ERK were also decreased by silencing of DDX10. Therefore, Silencing of DDX10 inhibited proliferation, invasion and migration of MG63 cells, which might be regulated by suppression of MAPK pathway. In conclusion, our results unfold a novel area of studying for understanding how DDX10 functions in OS oncogenic and prognostic significance, accordingly implying a promising therapeutic target for OS treatment.
骨肉瘤（OS）是一种侵袭性的骨骼系统癌症。其病因和发病机制的分子机制尚不清楚，因此需要进一步研究 OS 的有效治疗策略。首先，我们根据 GEO 数据库获得的数据，分析了 RNA 解旋酶 DDX10 在 OS 患者中的表达水平和预后能力。接下来，我们使用 CCK8 测试 OS 细胞活力。此外，我们使用划痕愈合实验和 Transwell 迁移实验检测 OS MG63 细胞系的细胞迁移。并通过 Transwell 侵袭实验检测细胞侵袭。此外，我们使用 QRT-PCR 和 Western blot 分析了 mRNA 和蛋白表达水平。我们发现 DDX10 在 OS 患者中明显过表达，DDX10 水平升高与预后不良有关。DDX10 的沉默抑制了 MG63 细胞在体外的增殖、侵袭和迁移。下调 DDX10 抑制了 MAPK 信号通路。沉默 DDX10 还降低了 p-MEK 和 p-ERK 的表达。因此，沉默 DDX10 抑制了 MG63 细胞的增殖、侵袭和迁移，这可能是通过抑制 MAPK 通路来调节的。总之，我们的研究结果为理解 DDX10 在骨肉瘤致癌和预后意义中的作用开辟了一个新的研究领域，从而为 OS 的治疗提供了一个有前途的治疗靶点。
