Related Experiment Video
Updated: Sep 4, 2025
Analysis of Retinoic Acid-induced Neural Differentiation of Mouse Embryonic Stem Cells in Two and Three-dimensional Embryoid Bodies
Published on: April 22, 2017
DRR1 promotes neuroblastoma cell differentiation by regulating CREB expression
Luping Chen1, Bin Mu2, Yalong Li1
1Department of Physiology, Shenyang Medical College, Shenyang, Liaoning, P.R. China.
Background:
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.
Methods:
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.
Results:
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.
Conclusions:
DRR1-CREB axis modulates the differentiation of neuroblastoma cells and is associated with the outcome of neuroblastoma patients.
Impact:
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.
Insights
Downregulating DRR1 inhibits neuroblastoma cell differentiation. The DRR1-CREB axis is crucial for neuroblastoma differentiation and patient outcomes, offering potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Neuroblastoma is a common infant cancer and childhood extracranial solid tumor.
- Downregulation of DRR1 was observed in poorly differentiated neuroblastoma cells.
- The precise role of DRR1 in neuroblastoma pathogenesis was largely unknown.
Purpose of the Study:
- To investigate the role of DRR1 in neuroblastoma cell differentiation.
- To identify downstream targets of DRR1 involved in neuroblastoma development.
- To explore the therapeutic potential of the DRR1-CREB pathway.
Main Methods:
- Neuroblastoma cells were induced to differentiate, and DRR1 expression was analyzed.
- CRISPR interference (CRISPRi) and overexpression vectors were used to manipulate DRR1 and CREB levels.
- Chromatin immunoprecipitation sequencing (ChIP-seq) identified downstream genes of DRR1.
- Cell differentiation markers, cell cycle distribution, and tumor growth were assessed.
Main Results:
- DRR1 expression increased upon neuroblastoma cell differentiation.
- Downregulation of DRR1 impaired neuroblastoma cell differentiation.
- CREB was identified as a downstream mediator of DRR1's function in differentiation.
- Overexpression of CREB reversed the inhibitory effects of DRR1 knockdown on differentiation and tumor growth.
Conclusions:
- The DRR1-CREB axis plays a significant role in modulating neuroblastoma cell differentiation.
- This pathway is associated with patient prognosis in neuroblastoma.
- Targeting the DRR1-CREB interaction may offer a novel therapeutic strategy for neuroblastoma.
Related Concept Videos
02:23Abnormal Proliferation
01:23Negative Regulator Molecules