Knockdown of DNA methyltransferase-1 inhibits proliferation and derepresses tumor suppressor genes in myeloma cells

Abstract

DNA methyltransferases (including DNMT1, DNMT3A and DNMT3B), catalyze the transfer of methyl groups from S-adenosyl-l-methionine to cytosine position 5; this methylation in promoter regions silences gene expression. In addition, DNMT1 plays a critical role in the maintenance of genomic DNA methylation during DNA replication. In the present study, silencing of <i>DNMT1</i> with siRNA was performed in RPMI-8226 human multiple myeloma (MM) cells, and the impact on gene methylation status and proliferation of the cells was analyzed. Upon <i>DNMT1</i> downregulation, proliferation decreased significantly compared with that in the control, non-transfected cells. The expression of B-cell lymphoma 2 and nuclear factor κB proteins was also significantly reduced. Furthermore, nested methylation-specific polymerase chain reaction revealed that methylation of the tumor suppressor genes, suppressor of cytokine signaling 1 and <i>p16,</i> was significantly reduced upon DNMT1 knockdown. Our results suggest that <i>DNMT1</i> silencing may be a promising strategy to consider during development of novel MM treatment strategies.