hsa-miR-29b

acute myeloid leukemia (AML)

Relationship type:

Causal

Detection method for miRNA expression:

Northern blot, qRT-PCR etc

down-regulated

Validated targets of miRNA from the reference:

DNMT3A, DNMT3B, Sp1

Validated targets of miRNA from TarBase:

unknown : More...

Description:

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

Reference:

MicroRNA -29b induces global DNA hypomethylation and tumor suppressor gene re-expression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1. | PMID:19211935
Garzon R, Liu S, Fabbri M, Liu Z, Heaphy CE, Callegari E, Schwind S, Pang J, Yu J, Muthusamy N, Havelange V, Volinia S, Blum W, Rush LJ, Perrotti D, Andreeff M, Bloomfield CD, Byrd JC, Chan K, Wu LC, Croce CM, Marcucci G.
Blood. 2009 Feb 11. [Epub ahead of print]