title: The expression of RUNDC3B is associated with promoter methylation in lymphoid malignancies.
abstract: DNA methylation is an epigenetic modification that plays an important role in the regulation of gene expression. The function of RUNDC3B has yet to be determined, although its dysregulated expression has been associated with malignant potential of both breast and lung carcinoma. To elucidate the potential of using DNA methylation in RUNDC3B as a biomarker in lymphoid malignancies, the methylation status of six regions spanning the CpG island in the promoter region of RUNDC3B was determined in cancer cell lines. Lymphoid malignancies were found to have more prominent methylation and did not express RUNDC3B compared with myeloid malignancies and solid tumours, supporting the potential use of DNA methylation in this region as a biomarker for lymphoid malignancies. RUNDC3B contains a RUN domain in its N-terminal region that mediates interaction with Rap2, an important component of the mitogen-activated protein kinase (MAPK) cascade, which regulates cellular proliferation and differentiation. The protein sequence of RUNDC3B also contains characteristic binding sites for MAPK intermediates. Therefore, it is possible that RUNDC3B serves as a mediator between Rap2 and the MAPK signalling cascade. Three genes with MAPK-inducible expression were downregulated in a methylated leukaemia cell line (HSPA5, Jun and Fos). Jun and Fos combine to form the activating protein 1 transcription factor, and loss of this factor is associated with the dysregulation of genes involved in differentiation and proliferation. We hypothesize that the loss of RUNDC3B secondary to aberrant hypermethylation of the early growth response 3 transcription factor binding site results in dysregulated MAPK signalling and carcinogenesis in lymphoid malignancies. © 2015 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
authors.forename: Dane W
authors.initials: DW
authors.lastname: Burmeister
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.|Department of Dermatology, University of Michigan Health System, Ann Arbor, MI, USA.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Smith
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Cristel
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.|Department of Animal Science, University of Vermont, Burlington, VT, USA.
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: McKay
authors.affiliation: Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
authors.forename: Huidong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Arthur
authors.affiliation: Department of Health Management and Informatics, University of Missouri, Columbia, MO, USA.|Department of Statistics, University of Missouri, Columbia, MO, USA.
authors.forename: Justin Wade
authors.initials: JW
authors.lastname: Davis
authors.affiliation: Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
authors.forename: Kristen H
authors.initials: KH
authors.lastname: Taylor
mesh_terms: D000072283:A549 Cells; D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D000091342:Endoplasmic Reticulum Chaperone BiP; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D019169:Jurkat Cells; D007938:Leukemia / Q000378:metabolism; D020935:MAP Kinase Signaling System; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D000072417:Protein Domains; D020668:rap GTP-Binding Proteins / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C477805:RUNDC3B protein, human; C116756:RAP2A protein, human; D020668:rap GTP-Binding Proteins
keywords: B cell; DNA methylation; RUNDC3B; gene expression; leukaemia; lymphoma