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Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer.
Zhou, Stanley; Hawley, James R; Soares, Fraser; Grillo, Giacomo; Teng, Mona; Madani Tonekaboni, Seyed Ali; Hua, Junjie Tony; Kron, Ken J; Mazrooei, Parisa; Ahmed, Musaddeque; Arlidge, Christopher; Yun, Hwa Young; Livingstone, Julie; Huang, Vincent; Yamaguchi, Takafumi N; Espiritu, Shadrielle M G; Zhu, Yanyun; Severson, Tesa M; Murison, Alex; Cameron, Sarina; Zwart, Wilbert; van der Kwast, Theodorus; Pugh, Trevor J; Fraser, Michael; Boutros, Paul C; Bristow, Robert G; He, Housheng Hansen; Lupien, Mathieu.
Afiliación
  • Zhou S; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Hawley JR; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Soares F; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Grillo G; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Teng M; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Madani Tonekaboni SA; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Hua JT; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Kron KJ; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Mazrooei P; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Ahmed M; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Arlidge C; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Yun HY; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Livingstone J; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Huang V; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Yamaguchi TN; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
  • Espiritu SMG; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Zhu Y; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Severson TM; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Murison A; Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • Cameron S; Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • Zwart W; Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • van der Kwast T; Ontario Institute for Cancer Research, Toronto, ON, Canada.
  • Pugh TJ; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Fraser M; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Boutros PC; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Bristow RG; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • He HH; Division of Oncogenomics, Oncode Institute, the Netherlands Cancer Institute, Amsterdam, The Netherlands.
  • Lupien M; Laboratory of Chemical Biology and Institute for Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
Nat Commun ; 11(1): 441, 2020 01 23.
Article en En | MEDLINE | ID: mdl-31974375
Prostate cancer is the second most commonly diagnosed malignancy among men worldwide. Recurrently mutated in primary and metastatic prostate tumors, FOXA1 encodes a pioneer transcription factor involved in disease onset and progression through both androgen receptor-dependent and androgen receptor-independent mechanisms. Despite its oncogenic properties however, the regulation of FOXA1 expression remains unknown. Here, we identify a set of six cis-regulatory elements in the FOXA1 regulatory plexus harboring somatic single-nucleotide variants in primary prostate tumors. We find that deletion and repression of these cis-regulatory elements significantly decreases FOXA1 expression and prostate cancer cell growth. Six of the ten single-nucleotide variants mapping to FOXA1 regulatory plexus significantly alter the transactivation potential of cis-regulatory elements by modulating the binding of transcription factors. Collectively, our results identify cis-regulatory elements within the FOXA1 plexus mutated in primary prostate tumors as potential targets for therapeutic intervention.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Secuencias Reguladoras de Ácidos Nucleicos / Factor Nuclear 3-alfa del Hepatocito / Mutación Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Secuencias Reguladoras de Ácidos Nucleicos / Factor Nuclear 3-alfa del Hepatocito / Mutación Tipo de estudio: Prognostic_studies Límite: Humans / Male Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido