Start stocking the miRNA-29b in your medicine cabinet. A group of researchers from The Ohio State University recently cranked out some great data demonstrating how miRNAs work to regulate DNA methylation in acute myeloid leukemia (AML), outlining a potential therapeutic use of mir-29b.
The study reveals how miR-29b works by targeting DNA Methyltransferases (DNMTs), the administrators of methyl group donations in the nucleus. DNMTs have been found to be overexpressed in AML, leading to aberrant DNA hypermethylation and silencing of tumor suppressor genes. DNMTs are the some of the first epigenetic proteins to be targeted by approved therapeutics like 5-azacytidine (Vidaza®), and decitabine (Dacogen™).
Mir-29b was found to down-regulate DNMT3A and 3B by targeting them directly, as well as DNMT1 indirectly by targeting Sp1, one of its transcription factors.
Further experiments demonstrated that the over-expression of pre-miR-29b in AML led to reduced global DNA methylation, restored the expression of tumor suppressor genes ESR1 and P15INK4b, and induced partial differentiation and apoptosis.
The investigators conclude that because of its role in the regulation of DNA Methylation, DNMTs and tumor suppressor genes in AML, miR-29b has potential relevance as a therapeutic. The fact that miR-29b targets multiple DNMT isoforms leads the authors to “…envision that combining DNMT1 inhibitors (decitabine or azacitidine) with synthetic miR-29b oligonucleotides may result in a synergistic hypomethylating effect, more robust gene re-expression and in turn better disease response in AML.” For all of the details, see Blood, February. 2009