title: 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 ofDNMT1with 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. UponDNMT1downregulation, 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 andp16,was significantly reduced upon DNMT1 knockdown. Our results suggest thatDNMT1silencing may be a promising strategy to consider during development of novel MM treatment strategies.
authors.affiliation: Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361000, P.R. China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361000, P.R. China.
authors.forename: Huying
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361000, P.R. China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361000, P.R. China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Niu
authors.affiliation: Department of Hematology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361000, P.R. China.
authors.forename: Quanyi
authors.initials: Q
authors.lastname: Lu
keywords: DNA methyltransferases; myeloma cells; siRNA; tumor suppressor gene