title: Genome wide expression profiling of p53 regulated miRNAs in neuroblastoma.
abstract: 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.
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Ali
authors.initials: A
authors.lastname: Rihani
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Alan
authors.initials: A
authors.lastname: Van Goethem
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Maté
authors.initials: M
authors.lastname: Ongenaert
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: De Brouwer
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Pieter-Jan
authors.initials: PJ
authors.lastname: Volders
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Agarwal
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Katleen
authors.initials: K
authors.lastname: De Preter
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Mestdagh
authors.affiliation: Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Shohet
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Frank
authors.initials: F
authors.lastname: Speleman
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Jo
authors.initials: J
authors.lastname: Vandesompele
authors.affiliation: Center for Medical Genetics, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Van Maerken
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055106:Genome-Wide Association Study; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D035683:MicroRNAs / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D035683:MicroRNAs; D010879:Piperazines; D016159:Tumor Suppressor Protein p53; C482205:nutlin 3