DNA methylation and microRNA dysregulation in cancer.
DNA methylation plays a key role in the silencing of numerous cancer-related genes, thereby affecting a number of vital cellular processes, including the cell cycle checkpoint, apoptosis, signal transduction, cell adhesion and angiogenesis. Also widely altered in human malignancies is the expression of microRNAs (miRNAs), a class of small noncoding RNAs that act as posttranscriptional regulators of gene expression. Furthermore, emerging evidence now supports the idea that DNA methylation is crucially involved in the dysregulation of miRNAs in cancer. This is in part the result of technological advances that enable more comprehensive analysis of miRNA expression profiles and the epigenome in cancer cells, which has led to the identification of a number of epigenetically regulated miRNAs. As with protein-coding genes, it appears that miRNA genes involved in regulating cancer-related pathways are silenced in association with CpG island hypermethylation. In addition, methylation in CpG island shore regions and DNA hypomethylation also appear to contribute to miRNA dysregulation in cancer. Aberrant DNA methylation of miRNA genes is a potentially useful biomarker for detecting cancer and predicting its outcome. Moreover, re-expression of miRNAs and the replacement of tumor suppressive miRNAs using miRNA mimics or expression vectors could be effective approaches to cancer therapy.
Department of Molecular Biology, Sapporo Medical University, S1 W17, Chuo-Ku, Sapporo 060-8556, Japan. hsuzuki@sapmed.ac.jp
Hiromu
H
Suzuki
Reo
R
Maruyama
Eiichiro
E
Yamamoto
Masahiro
M
Kai
D000818:Animals; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009369:Neoplasms / Q000235:genetics* / Q000628:therapy
D035683:MicroRNAs; D004247:DNA