Chen Luping, Mu Bin, Li Yalong, Lu Fangjin, Mu Ping
Department of Physiology, Shenyang Medical College, Shenyang, Liaoning, P.R. China.
Shanghai Zhaohui Pharmaceutical Co. Ltd, Shanghai, P.R. China.
Pediatr Res. 2023 Mar;93(4):852-861. doi: 10.1038/s41390-022-02192-8. Epub 2022 Jul 19.
Neuroblastoma is the most common cancer in infants and the most common extracranial solid tumor in childhood. DRR1 was identified to be downregulated in poorly differentiated ganglion cells from neuroblastoma model mice. However, the roles of DRR1 in neuroblastoma remain largely unclear.
The neuroblastoma cells were induced to differentiate, and the expression of DRR1 was detected. The expression of the neuroblastoma cell differentiation markers was analyzed in DRR1 shRNA- or DRR1-expressing vector-treated neuroblastoma cells. The downstream genes of DRR1 were screened with ChIP-seq assay. Finally, TNB1 cells were infected with DRR1 shRNA and CREB expressing vector containing lentivirus, and the expression of the cell differentiation markers, cell cycle distribution and tumor growth were analyzed.
The expression of DRR1 was increased in differentiated neuroblastoma cells, and downregulation of DRR1 expression inhibited the differentiation of neuroblastoma cells. Further experiments indicated that CREB is a candidate downstream gene of DRR1, and it mediates neuroblastoma cell differentiation. Moreover, overexpression of CREB rescued the effect of DRR1 shRNA on cell differentiation, cell cycle distribution and tumor growth in neuroblastoma.
DRR1-CREB axis modulates the differentiation of neuroblastoma cells and is associated with the outcome of neuroblastoma patients.
DRR1 is involved in regulation of the differentiation of neuroblastoma. Binding with actin is essential for DRR1 to regulate neuroblastoma cell differentiation. CREB is a candidate downstream gene of DRR1 in regulating of the differentiation of neuroblastoma.
神经母细胞瘤是婴儿中最常见的癌症，也是儿童期最常见的颅外实体瘤。在神经母细胞瘤模型小鼠的低分化神经节细胞中，DRR1被鉴定为表达下调。然而，DRR1在神经母细胞瘤中的作用仍不清楚。
诱导神经母细胞瘤细胞分化，并检测DRR1的表达。在经DRR1短发夹RNA（shRNA）或表达DRR1的载体处理的神经母细胞瘤细胞中分析神经母细胞瘤细胞分化标志物的表达。通过染色质免疫沉淀测序（ChIP-seq）分析筛选DRR1的下游基因。最后，用携带DRR1 shRNA和表达CREB的载体的慢病毒感染TNB1细胞，并分析细胞分化标志物的表达、细胞周期分布和肿瘤生长情况。
在分化的神经母细胞瘤细胞中DRR1的表达增加，DRR1表达下调抑制神经母细胞瘤细胞的分化。进一步实验表明，CREB是DRR1的候选下游基因，它介导神经母细胞瘤细胞的分化。此外，CREB的过表达挽救了DRR1 shRNA对神经母细胞瘤细胞分化、细胞周期分布和肿瘤生长的影响。
DRR1-CREB轴调节神经母细胞瘤细胞的分化，并与神经母细胞瘤患者的预后相关。
DRR1参与神经母细胞瘤分化的调控。与肌动蛋白结合对DRR1调节神经母细胞瘤细胞分化至关重要。CREB是DRR1在调节神经母细胞瘤分化中的候选下游基因。
