Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives

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 lea...

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Bibliographic Details
Published in:International journal of molecular sciences 2012-12, Vol.13 (12), p.16554-16579
Main Authors: Romania, Paolo, Bertaina, Alice, Bracaglia, Giorgia, Locatelli, Franco, Fruci, Doriana, Rota, Rossella
Format: Article
Language:English
Subjects:
Adolescent
Adult
Child
Child, Preschool
differentiation
DNA methylation
Epigenesis, Genetic
epigenetics
histones
Humans
Infant
microRNA
MicroRNAs - biosynthesis
MicroRNAs - genetics
neuroblastoma
Neuroblastoma - genetics
Neuroblastoma - metabolism
Neuroblastoma - pathology
Polycomb proteins
Review
rhabdomyosarcoma
Rhabdomyosarcoma - genetics
Rhabdomyosarcoma - metabolism
Rhabdomyosarcoma - pathology
RNA, Neoplasm - biosynthesis
RNA, Neoplasm - genetics
Translational Medical Research
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms131216554