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Bromodomain and extra-terminal domain inhibition modulates the expression of pathologically relevant microRNAs in diffuse large B-cell lymphoma.
Mensah, Afua A; Cascione, Luciano; Gaudio, Eugenio; Tarantelli, Chiara; Bomben, Riccardo; Bernasconi, Elena; Zito, Domenico; Lampis, Andrea; Hahne, Jens C; Rinaldi, Andrea; Stathis, Anastasios; Zucca, Emanuele; Kwee, Ivo; Gattei, Valter; Valeri, Nicola; Riveiro, Maria E; Bertoni, Francesco.
Afiliação
  • Mensah AA; Università della Svizzera italiana (USI), Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Cascione L; Università della Svizzera italiana (USI), Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Gaudio E; Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
  • Tarantelli C; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Bomben R; Università della Svizzera italiana (USI), Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Bernasconi E; Università della Svizzera italiana (USI), Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Zito D; Clinical and Experimental Onco-Hematology Unit, Centro di Riferimento Oncologico, Aviano, Italy.
  • Lampis A; Università della Svizzera italiana (USI), Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Hahne JC; The Institute of Cancer Research, London, UK.
  • Rinaldi A; The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
  • Stathis A; The Institute of Cancer Research, London, UK.
  • Zucca E; The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
  • Kwee I; The Institute of Cancer Research, London, UK.
  • Gattei V; The Royal Marsden NHS Foundation Trust, London and Surrey, UK.
  • Valeri N; Università della Svizzera italiana (USI), Institute of Oncology Research (IOR), Bellinzona, Switzerland.
  • Riveiro ME; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
  • Bertoni F; Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Haematologica ; 103(12): 2049-2058, 2018 12.
Article em En | MEDLINE | ID: mdl-30076183
Aberrant changes in microRNA expression contribute to lymphomagenesis. Bromodomain and extra-terminal domain inhibitors such as OTX015 (MK-8628, birabresib) have demonstrated preclinical and clinical activity in hematologic tumors. MicroRNA profiling of diffuse large B-cell lymphoma cells treated with OTX015 revealed changes in the expression levels of a limited number of microRNAs, including miR-92a-1-5p, miR-21-3p, miR-155-5p and miR-96-5p. Analysis of publicly available chromatin immunoprecipitation sequencing data of diffuse large B-cell lymphoma cells treated with bromodomain and extra-terminal domain (BET) inhibitors showed that the BET family member BRD4 bound to the upstream regulatory regions of multiple microRNA genes and that this binding decreased following BET inhibition. Alignment of our microRNA profiling data with the BRD4 chromatin immunoprecipitation sequencing data revealed that microRNAs downregulated by OTX015 also exhibited reduced BRD4 binding in their promoter regions following treatment with another bromodomain and extra-terminal domain inhibitor, JQ1, indicating that BRD4 contributes directly to microRNA expression in lymphoma. Treatment with bromodomain and extra-terminal domain inhibitors also decreased the expression of the arginine methyltransferase PRMT5, which plays a crucial role in B-cell transformation and negatively modulates the transcription of miR-96-5p. The data presented here indicate that in addition to previously observed effects on the expression of coding genes, bromodomain and extra-terminal domain inhibitors also modulate the expression of microRNAs involved in lymphomagenesis.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Nucleares / Regulação Neoplásica da Expressão Gênica / Linfoma Difuso de Grandes Células B / Perfilação da Expressão Gênica / MicroRNAs / Domínios Proteicos Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Proteínas Nucleares / Regulação Neoplásica da Expressão Gênica / Linfoma Difuso de Grandes Células B / Perfilação da Expressão Gênica / MicroRNAs / Domínios Proteicos Limite: Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article