The Role of miR-124 in Neuroblastoma
Date Issued
2010
Date
2010
Author(s)
Chen, Cheng-Yu
Abstract
Neuroblastoma (NB) is an embryonic cancer of the postganglionic sympathetic nervous system, which is the most common tumor in children less than one year of age. Myc myelocytomatosis viral related oncogene, neuroblastoma derived (MYCN) amplification is known to be a marker of poor prognosis in NB patients. Our previous study found that N-myc expression level was inversely correlated with aryl hydrocarbon receptor (AHR). MicroRNAs have recently emerged as important regulators that play a significant role in tumorigenesis. In this study, gain-and loss-of-function analyses of miR-124 showed that miR-124 negatively regulated endogenous AHR protein expression in tumor cells. Anti-miR-124 inhibitor treatment decreased N-myc mRNA expression. MYCN has also been reported to prevent normal induction of neuroblast differentiation. Surprisingly, we observed changes in cellular morphology after inhibiting the endogenous miR-124 in SK-N-SH cell line. We also found that several cell differentiation markers, i.e. growth-associated protein 43 (GAP-43), calreticulin (CRT) and neuron-specific enolase (NSE) were up-regulated after anti-miR-124 treatment. It is possible that miR-124 suppression causes AHR up-regulation and MYCN down-regulation, resulting in cell differentiation. Our data suggest that miR-124 may play an important role in neuroblastoma cell differentiation and serve as a potential target for neuroblastoma therapy.
Subjects
Neuroblastoma
MYCN
AHR
miR-124
differentiation
SDGs
Type
thesis
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