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The expression of RUNDC3B is associated with promoter methylation in lymphoid malignancies.
Burmeister, Dane W; Smith, Emily H; Cristel, Robert T; McKay, Stephanie D; Shi, Huidong; Arthur, Gerald L; Davis, Justin Wade; Taylor, Kristen H.
Afiliación
  • Burmeister DW; Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
  • Smith EH; Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
  • Cristel RT; Department of Dermatology, University of Michigan Health System, Ann Arbor, MI, USA.
  • McKay SD; Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
  • Shi H; Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
  • Arthur GL; Department of Animal Science, University of Vermont, Burlington, VT, USA.
  • Davis JW; Department of Biochemistry and Molecular Biology, Georgia Regents University, Augusta, GA, USA.
  • Taylor KH; Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO, USA.
Hematol Oncol ; 35(1): 25-33, 2017 Mar.
Article en En | MEDLINE | ID: mdl-26011749
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Portadoras / Regulación Neoplásica de la Expresión Génica / Regiones Promotoras Genéticas / Neoplasias Hematológicas / Metilación de ADN / Proteínas del Tejido Nervioso Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Hematol Oncol Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Portadoras / Regulación Neoplásica de la Expresión Génica / Regiones Promotoras Genéticas / Neoplasias Hematológicas / Metilación de ADN / Proteínas del Tejido Nervioso Tipo de estudio: Risk_factors_studies Límite: Humans Idioma: En Revista: Hematol Oncol Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido