title: Decitabine represses translocated MYC oncogene in Burkitt lymphoma.
abstract: Burkitt lymphoma (BL) is caused by translocation of the MYC gene to an immunoglobulin locus resulting in its constitutive expression depending on the activity of the immunoglobulin (Ig) enhancer elements. Treatment of BL cell lines with epigenetic modifiers is known to repress B-cell-specific genes and to up-regulate B-cell-inappropriate genes including the transcription repressor ID2 expression. We found that the DNA methyltransferase inhibitor decitabine/5-aza-2-deoxycytidine (5-aza-dC) represses the MYC oncogene on RNA and protein levels by inducing ID2. Down-regulation of MYC was associated with repression of transcriptional activity of the Ig locus and with inhibition of proliferation. The induction of ID2 can be in part explained by activation of the transcription factor NF-κB. We conclude that up-regulation of ID2 contributes to anti-tumour activity of 5-aza-dC via repression of Ig locus activity and consequently MYC expression.
authors: Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, HuaZhong University of Science and Technology, Wuhan, China.
authors: Hanfeng
authors: H
authors: Guan
authors: Linka
authors: L
authors: Xie
authors: Kay
authors: K
authors: Klapproth
authors: Clarissa D
authors: CD
authors: Weitzer
authors: Thomas
authors: T
authors: Wirth
authors: Alexey
authors: A
authors: Ushmorov
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D063185:Epigenetic Repression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014178:Translocation, Genetic / Q000187:drug effects*; D015854:Up-Regulation
chemical_list: D000964:Antimetabolites, Antineoplastic; C497450:ID2 protein, human; D007075:Immunoglobulin M; D051797:Inhibitor of Differentiation Protein 2; C489427:MYC protein, human; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine