MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1.

摘要: Aberrant DNA hypermethylation contributes to myeloid leukemogenesis by silencing structurally normal genes involved in hematopoiesis. MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression targeting protein-coding mRNAs. Recently, miRNAs have been shown play a role as both targets and effectors malignant cells. In the current study, we showed enforced of miR-29b acute leukemia cells resulted marked reduction methyltransferases DNMT1, DNMT3A, DNMT3B at RNA protein levels. This turn led decrease global methylation reexpression p15(INK4b) ESR1 via promoter hypomethylation. Although down-regulation DNMT3A was result direct interaction with 3' untranslated regions these genes, no predicted sites were found DNMT1 regions. Further experiments revealed down-regulates indirectly Sp1, transactivator gene. Altogether, data provide novel functional links between aberrant suggest potentially therapeutic use synthetic oligonucleotides effective hypomethylating compounds.