DRR1调节神经母细胞瘤细胞分化的作用机制

The mechanism of DRR1 on the regulation of neuroblastoma cell differentiation

目的:探究肾细胞癌下调蛋白1(down-regulated in renal cell carcinoma 1,DRR1)在神经母细胞瘤细胞分化中的作用以及内在的分子机制。方法:在神经母细胞瘤细胞中敲减或过表达DRR1后,分别考察细胞分化状态的变化、细胞周期的变化以及利用real-time PCR的方法检测其潜在下游因子的表达变化;利用神经母细胞瘤患者数据库,分析在神经母细胞瘤患者样本中DRR1的潜在下游因子的表达与DRR1表达之间的相关性;诱导神经母细胞瘤细胞分化后,利用real-time PCR的方法检测DRR1的潜在下游因子的表达变化。结果:DRR1的表达可促进神经母细胞瘤细胞的分化;敲减DRR1促进神经母细胞瘤细胞的G_(1)/S期的转换,过表达DRR1抑制神经母细胞瘤细胞的G_(1)/S期的转换;DRR1的表达改变影响其潜在下游因子在神经母细胞瘤细胞中的表达;在神经母细胞瘤患者样本中DRR1的表达与其潜在下游因子的表达呈显著相关性;DRR1的潜在下游因子的表达随神经母细胞瘤细胞分化状态的变化而改变。结论:DRR1通过调控下游因子的表达调节神经母细胞瘤细胞的分化。

Objective:To explore the role and the mechanism of DRR1 on the neuroblastoma cell differentiation.Methods:To analyze the cell differentiation status,the cell cycle and the expression of the candidate downstream genes of DRR1 in DRR1 overexpressed or DRR1 knocked down neuroblastoma cells.To analyze the correlation of the expression of DRR1 and the expression of its candidate downstream genes in neuroblastoma patients'database.To analyze the expression of the candidate downstream genes of DRR1 in neuroblastoma cells after the differentiation induction.Results:Overexpression of DRR1 promoted the differentiation of neuroblastoma cells.Downregulation of DRR1 promoted the G_(1)/S transition,and overexpression of DRR1 suppressed the G_(1)/S transition in neuroblastoma cells.The expression of the candidate downstream genes of DRR1 was changed in DRR1 overexpressed neuroblastoma cells.There was significant correlation between the expression of DRR1 and the expression of its candidate downstream genes in the clinical neuroblastoma patients'database.The expression of the candidate downstream genes of DRR1 was changed according to the differentiation status of neuroblastoma cells.Conclusion:DRR1 regulates cell differentiation in neuroblastoma by modulating the expression of its downstream genes.