Tumor-suppressive microRNA silenced by tumor-specific DNA hypermethylation in cancer cells

MicroRNA (miRNA) genes, located in intergenic or intragenic non-coding regions of the genome, are transcribed and processed to small non-protein-coding RNA of approximately 22 nucleotides negatively regulating gene expression. Some miRNA have already been reported for their genetic alterations, aberrant expression and oncogenic or tumor-suppressive functions. After 2008, there has been a striking increase in the number of publications reporting tumor-suppressive miRNA (TS-miRNA) silenced epigenetically in various types of cancers, suggesting important clinical applications for miRNA-based molecular diagnosis and therapy for cancers. Here, we introduce a correlation of the gene silencing of TS-miRNA through CpG island hypermethylation with the genomic distances between intergenic and intragenic miRNA genes or protein-coding host genes and CpG islands located around these genes. Furthermore, we also discuss the potential of miRNA replacement therapy for cancers using double-stranded RNA mimicking TS-miRNA. (Cancer Sci 2012; 103: 837845)