Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives

Research output: Contribution to journalArticle

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

Fingerprint

Deregulation
Rhabdomyosarcoma
MicroRNAs
Neuroblastoma
Epigenomics
Tumors
tumors
chromatin
cancer
Tissue
Neoplasms
Chromatin Assembly and Disassembly
suppressors
skeletal muscle
Pediatrics
gene expression
Chromatin
Gene expression
genes
markers

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)

Cite this

@article{bebaf757400a412b802260c1dd217cd1,
title = "Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives",
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 = "Differentiation, DNA methylation, Epigenetics, Histones, MicroRNA, Neuroblastoma, Polycomb proteins, Rhabdomyosarcoma",
author = "Paolo Romania and Alice Bertaina and Giorgia Bracaglia and Franco Locatelli and Doriana Fruci and Rossella Rota",
year = "2012",
doi = "10.3390/ijms131216554",
language = "English",
volume = "13",
pages = "16554--16579",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "12",

}

TY - JOUR

T1 - Epigenetic deregulation of microRNAs in rhabdomyosarcoma and neuroblastoma and translational perspectives

AU - Romania, Paolo

AU - Bertaina, Alice

AU - Bracaglia, Giorgia

AU - Locatelli, Franco

AU - Fruci, Doriana

AU - Rota, Rossella

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Differentiation

KW - DNA methylation

KW - Epigenetics

KW - Histones

KW - MicroRNA

KW - Neuroblastoma

KW - Polycomb proteins

KW - Rhabdomyosarcoma

UR - http://www.scopus.com/inward/record.url?scp=84871675120&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871675120&partnerID=8YFLogxK

U2 - 10.3390/ijms131216554

DO - 10.3390/ijms131216554

M3 - Article

C2 - 23443118

AN - SCOPUS:84871675120

VL - 13

SP - 16554

EP - 16579

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 12

ER -