title: Epigenetic inactivation of the MIR34B/C in multiple myeloma.
abstract: We postulated that MIR34B/C, a direct transcriptional target of TP53, might be inactivated by promoter hypermethylation in multiple myeloma (MM). MIR34B/C promoter methylation was studied in 8 normal marrow controls, 8 MM cell lines, 95 diagnostic, and 23 relapsed/progressed MM samples by methylation-specific PCR. MIR34B/C was methylated in 6 (75.0%) MM cell lines but not normal controls. 5-Aza-2'-deoxycytidine led to MIR34B/C promoter demethylation and MIR34B reexpression. Moreover, restoration of MIR34B led to reduced cellular proliferation and enhanced apoptosis of myeloma cells. In primary samples, methylation of MIR34B/C occurred in 5.3% at diagnosis and 52.2% at relapse/disease progression (P < .001). In 12 MM patients with paired samples at diagnosis and relapse/progression, MIR34B/C methylation was acquired in 6 at relapse/progression. In conclusion, MIR34B/C is a tumor suppressor in myeloma. Hypermethylation of MIR34B/C is tumor-specific. Frequent MIR34B/C hypermethylation during relapse/progression but not at diagnosis implicated a role of MIR34B/C hypermethylation in myeloma relapse/progression.
authors: Department of Medicine, Queen Mary Hospital, University of Hong King, Pokfulam, Hong Kong.
authors: Kwan Yeung
authors: KY
authors: Wong
authors: Rita Lok Hay
authors: RL
authors: Yim
authors: Chi Chiu
authors: CC
authors: So
authors: Dong-Yan
authors: DY
authors: Jin
authors: Raymond
authors: R
authors: Liang
authors: Chor Sang
authors: CS
authors: Chim
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D019175:DNA Methylation; D000077209:Decitabine; D018450:Disease Progression; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D061251:Primary Cell Culture; D012008:Recurrence; D014407:Tumor Cells, Cultured
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D000077209:Decitabine; D001374:Azacitidine