Restoration of the antitumor activity of p53 could offer a promising approach for the treatment of
neuroblastoma.
MicroRNAs (
miRNAs) are important mediators of p53 activity, but their role in the p53 response has not yet been comprehensively addressed in
neuroblastoma. Therefore, we set out to characterize alterations in
miRNA expression that are induced by p53 activation in
neuroblastoma cells. Genome-wide
miRNA expression analysis showed that miR-34a-5p, miR-182-5p, miR-203a, miR-222-3p, and miR-432-5p are upregulated following
nutlin-3 treatment in a p53 dependent manner. The function of miR-182-5p, miR-203a, miR-222-3p, and miR-432-5p was analyzed by ectopic overexpression of
miRNA mimics. We observed that these p53-regulated
miRNAs inhibit the proliferation of
neuroblastoma cells to varying degrees, with the most profound growth inhibition recorded for miR-182-5p. Overexpression of miR-182-5p promoted apoptosis in some
neuroblastoma cell lines and induced neuronal differentiation of NGP cells. Using
Chromatin Immunoprecipitation-qPCR (ChIP-qPCR), we did not observe direct binding of p53 to MIR182, MIR203, MIR222, and MIR432 in
neuroblastoma cells. Taken together, our findings yield new insights in the network of p53-regulated
miRNAs in
neuroblastoma.