Epigenetic alterations and microRNA misexpression in cancer and autoimmune diseases: a critical review

Yoshimasa Saito, Hidetsugu Saito, Gangning Liang, Jeffrey M. Friedman

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Epigenetic markers such as DNA methylation and histone modifications around promoter regions modify chromatin structure and regulate expression of downstream genes. In fact, aberrant epigenetic modifications are common events in human disease including tumorigenesis and autoimmunity. Small non-coding RNAs named microRNAs (miRNAs) are modulators of gene expression and play critical roles in various cellular processes. Several miRNAs have been characterized as tumor suppressors or oncogenes in cancer, and recent reports implicate certain miRNAs in the pathogenesis of autoimmune diseases. Epigenetic investigations have shown that distinct miRNAs are directly regulated by DNA methylation and histone modifications at their promoters. Moreover, miRNAs themselves are key participants in regulating the chromatin modifying machinery. Chromatin-modifying drugs such as DNA methylation inhibitors and histone deacetylase inhibitors have shown efficacy in human malignancies and there is some evidence that these drugs may be useful in autoimmune disease. The benefits of these drugs are at least partially mediated by restoring expression of epigenetically silenced tumor suppressor genes, including miRNAs. The complex layers regulating gene expression have yet to be fully elucidated, but it is clear that epigenetic alterations and miRNA misexpression are essential events in pathologic processes, especially cancer and autoimmune disease, and represent promising therapeutic targets.

Original languageEnglish
Pages (from-to)128-135
Number of pages8
JournalClinical reviews in allergy & immunology
Volume47
Issue number2
DOIs
Publication statusPublished - 2014 Oct 1

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this