Background/ Aims:
Retinoic acid (RA) is used for the treatment of high-risk neuroblastoma patient, but the prognosis remains unsatisfied for the arising of drug resistance during treatment. MicroRNAs (miRNAs) are small RNAs with 19-23 nt in length and function as a master regulator in cellular signaling pathways. In this research, we aimed to investigate the miRNA signature that specifically exists in RA-resistant (RAR) neuroblastoma cells.
Materials and Methods:
RAR neuroblastoma cells were selected through repeated treatment of RA, with 25 micro-molar as the selection endpoint. The RNA extracted from control and RAR cells were subjected to Affymetrix miRNA 4.0 array. The results were analyzed with software Expression Console and Transcriptome Analysis Console.
Results:
After the selection procedure, RAR cells showed higher tolerance to RA treatment than control cells (Figure 1A). The array data revealed that 114 miRNAs have significantly different expression level (5-fold difference) in RAR cells compared to control (Figure 1B). The potential target of these miRNAs comprises genes essential for regulating cell cycle, proliferation, stress response, and drug metabolism. The significance of these miRNAs and their respective targets in RA resistance are currently under validated.
Conclusion:
Our results suggested that aberrant miRNA expression may represent the molecular signature for RA resistance. By targeting these miRNAs we would find novel treatment strategies for RA-resistant neuroblastomas.
Figure 1