Methylation of tumor suppressor microRNAs: lessons from lymphoid malignancies

Abstract

miRNAs are a group of small noncoding RNAs measuring 19–25 nucleotides. Sequence-specific binding of miRNAs to the 3´ untranslated regions of target genes leads to translational repressions. Dysregulation of miRNA expression involved in cancer can be triggered by multiple mechanisms including aberrant DNA methylation of the miRNA gene promoter. Of note, DNA methylation of tumor suppressor miRNAs has been implicated in various human cancers. Moreover, miRNA silencing mediated by aberrant promoter DNA methylation can potentially be reversed by hypomethylating agents, and hence may pose a new therapeutic target in cancer. In this review, the authors will focus on the aberrant methylation of miRNAs in the pathogenesis of lymphoid malignancies including chronic lymphocytic leukemia, multiple myeloma and acute lymphoblastic leukemia.