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Int. J. Mol. Sci. 2012, 13(12), 16554-16579; doi:10.3390/ijms131216554

Epigenetic Deregulation of MicroRNAs in Rhabdomyosarcoma and Neuroblastoma and Translational Perspectives

1
Department of Pediatric Hematology-Oncology, Ospedale Pediatrico Bambino Gesù, IRCCS, Piazza S. Onofrio 4, Roma 00165, Italy
2
Department of Pediatric Sciences, University of Pavia, Corso Strada Nuova 65, Pavia I-27100, Italy
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 29 October 2012 / Revised: 21 November 2012 / Accepted: 21 November 2012 / Published: 5 December 2012
(This article belongs to the Special Issue Non-Coding RNAs 2012)
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Abstract

Gene expression control mediated by microRNAs and epigenetic remodeling of chromatin are interconnected processes often involved in feedback regulatory loops, which strictly guide proper tissue differentiation during embryonal development. Altered expression of microRNAs is one of the mechanisms leading to pathologic conditions, such as cancer. Several lines of evidence pointed to epigenetic alterations as responsible for aberrant microRNA expression in human cancers. Rhabdomyosarcoma and neuroblastoma are pediatric cancers derived from cells presenting features of skeletal muscle and neuronal precursors, respectively, blocked at different stages of differentiation. Consistently, tumor cells express tissue markers of origin but are unable to terminally differentiate. Several microRNAs playing a key role during tissue differentiation are often epigenetically downregulated in rhabdomyosarcoma and neuroblastoma and behave as tumor suppressors when re-expressed. Recently, inhibition of epigenetic modulators in adult tumors has provided encouraging results causing re-expression of anti-tumor master gene pathways. Thus, a similar approach could be used to correct the aberrant epigenetic regulation of microRNAs in rhabdomyosarcoma and neuroblastoma. The present review highlights the current insights on epigenetically deregulated microRNAs in rhabdomyosarcoma and neuroblastoma and their role in tumorigenesis and developmental pathways. The translational clinical implications and challenges regarding modulation of epigenetic chromatin remodeling/microRNAs interconnections are also discussed.
Keywords: microRNA; rhabdomyosarcoma; neuroblastoma; epigenetics; differentiation; Polycomb proteins; DNA methylation; histones microRNA; rhabdomyosarcoma; neuroblastoma; epigenetics; differentiation; Polycomb proteins; DNA methylation; histones
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Romania, P.; Bertaina, A.; Bracaglia, G.; Locatelli, F.; Fruci, D.; Rota, R. Epigenetic Deregulation of MicroRNAs in Rhabdomyosarcoma and Neuroblastoma and Translational Perspectives. Int. J. Mol. Sci. 2012, 13, 16554-16579.

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