Aberrant DNA methylation plays a relevant role in multiple myeloma (MM) 
pathogenesis. MicroRNAs (miRNAs) are a class of small non-coding RNAs that 
recently emerged as master regulator of gene expression by targeting 
protein-coding mRNAs. However, miRNAs involvement in the regulation of the 
epigenetic machinery and their potential use as therapeutics in MM remain to be 
investigated. Here, we provide evidence that the expression of de novo DNA 
methyltransferases (DNMTs) is deregulated in MM cells. Moreover, we show that 
miR-29b targets DNMT3A and DNMT3B mRNAs and reduces global DNA methylation in MM 
cells. In vitro transfection of MM cells with synthetic miR-29b mimics 
significantly impairs cell cycle progression and also potentiates the 
growth-inhibitory effects induced by the demethylating agent 5-azacitidine. Most 
importantly, in vivo intratumor or systemic delivery of synthetic miR-29b 
mimics, in two clinically relevant murine models of human MM, including the 
SCID-synth-hu system, induces significant anti-tumor effects. All together, our 
findings demonstrate that aberrant DNMTs expression is efficiently modulated by 
tumor suppressive synthetic miR-29b mimics, indicating that methyloma modulation 
is a novel matter of investigation in miRNA-based therapy of MM.