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.
Department of Molecular Cytogenetics, Tokyo Medical and Dental University, Tokyo, Japan.
Ken-ichi
K
Kozaki
Johji
J
Inazawa
D018797:Cell Cycle Proteins; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D020868:Gene Silencing; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D009369:Neoplasms / Q000235:genetics*; D015513:Oncogene Proteins; D010088:Oxidoreductases
D018797:Cell Cycle Proteins; D035683:MicroRNAs; D015513:Oncogene Proteins; D010088:Oxidoreductases; C486677:STEAP3 protein, human