Genome Wide Expression Profiling of P53 Regulated MiRNAs in Neuroblastoma

Overview

Journal Sci Rep

Specialty Science

Date 2015 Mar 13

PMID 25762502

Citations 21

Authors

Ali Rihani

Alan Van Goethem

Mate Ongenaert

Sara De Brouwer

Pieter-Jan Volders

Saurabh Agarwal

Katleen De Preter

Pieter Mestdagh

Jason Shohet

Frank Speleman

Jo Vandesompele

Tom Van Maerken

Affiliations

Soon will be listed here.

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.

Citing Articles

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Longitudinal evaluation of serum microRNAs as biomarkers for neuroblastoma burden and therapeutic p53 reactivation.

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