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Background: DNA methylation-mediated epigenetic silencing of microRNA is a critical event during the pathogenesis of diffuse large B cell lymphoma(DLBCL).Accumulating evidence has supported that low levels of miR-34a in DLBCLwere largely attributed to its aberrant hypermethylation.Diosgenin is a steroidal sapogenin, which is extracted from the tubers of Dioscorea wild yam, such as the Kokoro.Diosgenin possesses anti-cancer activities possibly via proliferation reduction, cell cycle arrest, and apoptosis induction.In addition, its chemopreventive role in DLBCLhas been reported recently.However, the cancer prevention activities of Diosgenin and the epigenetic-based effects in DLBCLremain largely unknown.In this study, we test the hypothesis that Diosgenin could play anti-proliferative effect on DLBCLcells through demethylation of miR-34a.Material and Methods: B lymphoblastoid cell lines (LCLs)and DLBCLcell lines(Oci-Ly10)were investigated by methylation and the expression of miR-34a using methylation-specific PCR(MSP)and real time-PCR(RT-PCR).The proliferation of Oci-Ly10 cells after Diosgenin treatment was measured using MTSproliferation assay.The methylation status and the expression of miR-34a were assessed using MSPand RTPCRin Oci-Ly10 cells after Diosgenin treatment.Result: In comparison with LCLs cells, hypermethylation of miR-34a was detected in Oci-Ly10 cells.The expression of miR-34a was significantly down-regulated in Oci-Ly10 cells when compared to LCLs ceils.Diosgenin treatment led to inhibition of proliferation in Oci-Ly10 cells as measured by the MTSassay.Compared to untreated Oci-Ly10 cells, the expression of miR-34a was significantly up-regulated through demethylation of miR-34a in Diosgenin treated Oci-Ly10 cells.Conclusion: In this study, we demonstrate that expression of miR-34a is frequently decreased in diffuse large B cell lymphoma (DLBCL)because of DNA hypermethylation.Diosgenin, a dietary compound, plays anti-proliferative effect on DLBCLcells through demethylation of miR-34a.Our findings not only provide preclinical evidence to demonstrate the use of Diosgenin as a dietary supplement to inhibit DLBCLbut also shed novel light on miR-34a as an epigenetic target for DLBCLprevention.These observations suggest that the therapeutic potential of Diosgenin, a novel, safe, and epigenetic agent, to be used in addition to chemotherapy for DLBCLpatients.