Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives

Paolo Romania, Alice Bertaina, Giorgia Bracaglia, Franco Locatelli, Doriana Fruci, Rossella Rota

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)16554-16579
Number of pages26
JournalInternational Journal of Molecular Sciences
Volume13
Issue number12
DOIs
Publication statusPublished - 2012

Keywords

  • Differentiation
  • DNA methylation
  • Epigenetics
  • Histones
  • MicroRNA
  • Neuroblastoma
  • Polycomb proteins
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Spectroscopy
  • Inorganic Chemistry
  • Catalysis
  • Molecular Biology
  • Computer Science Applications
  • Medicine(all)

Fingerprint Dive into the research topics of 'Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives'. Together they form a unique fingerprint.

Cite this