DNA Methylation of Tumor Suppressive miRNAs in Non-Hodgkin's Lymphomas

DNA methylation is an epigenetic alteration leading to heritable phenotypic changes of cells with functional consequences. It is important in early embryonic development, stem cell differentiation, and tissue-specific gene expression. In normal cells, promoter-associated CpG islands (CGI) are generally unmethylated except in X-chromosome inactivation or genomic imprinting. In cancer, tumor cells are characterized by global hypomethylation but locus-specific hypermethylation of promoter-associated CGI, resulting in gene silencing. MicroRNAs (miRNAs) are short, non-coding RNA sequences of 18-25 nucleotides, which can repress the translational of multiple protein-coding mRNAs by sequence-specific binding to the 3'untranslated region. Depending on the genes targeted, miRNA can be tumor suppressive if an oncogene is repressed, or it can be oncogenic when a tumor suppressive gene is repressed. Recently, aberrant methylation of tumor suppressive miRNAs has been reported in different types of cancers including lymphomas. Herein, we review the recent literature of methylation of tumor suppressive miRNAs in different histopathologic subtypes of lymphomas, and discuss its potential diagnostic, prognostic, and therapeutic significance.