Epigenetic inactivation of the MIR34B/C in multiple myeloma
Copyright policy )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.
- University of Hong Kong (香港大學) China (People's Republic of)
- Queen Mary Hospital China (People's Republic of)
- Hospital Authority China (People's Republic of)
- University of Hong Kong China (People's Republic of)
Azacitidine - Analogs & Derivatives - Pharmacology, Neoplastic - Drug Effects, Molecular Sequence Data, Primary Cell Culture, Gene Silencing - Drug Effects - Physiology, Decitabine, Dna Methylation, Epigenesis, Genetic, Multiple Myeloma - Genetics - Pathology, Recurrence, Tumor Cells, Cultured, Humans, Gene Silencing, Gene Expression Regulation, Neoplastic - Drug Effects, Genetic - Drug Effects - Physiology, Cultured, Base Sequence, DNA Methylation, Tumor Cells, Gene Expression Regulation, Neoplastic, Epigenesis, Genetic - Drug Effects - Physiology, MicroRNAs, Gene Expression Regulation, Azacitidine, Disease Progression, Micrornas - Genetics, Multiple Myeloma, Epigenesis
Azacitidine - Analogs & Derivatives - Pharmacology, Neoplastic - Drug Effects, Molecular Sequence Data, Primary Cell Culture, Gene Silencing - Drug Effects - Physiology, Decitabine, Dna Methylation, Epigenesis, Genetic, Multiple Myeloma - Genetics - Pathology, Recurrence, Tumor Cells, Cultured, Humans, Gene Silencing, Gene Expression Regulation, Neoplastic - Drug Effects, Genetic - Drug Effects - Physiology, Cultured, Base Sequence, DNA Methylation, Tumor Cells, Gene Expression Regulation, Neoplastic, Epigenesis, Genetic - Drug Effects - Physiology, MicroRNAs, Gene Expression Regulation, Azacitidine, Disease Progression, Micrornas - Genetics, Multiple Myeloma, Epigenesis
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