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X chromosome protects against bladder cancer in females via a KDM6A-dependent epigenetic mechanism.
Kaneko, Satoshi; Li, Xue.
Afiliação
  • Kaneko S; Department of Urology and Surgery, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
  • Li X; Department of Urology and Surgery, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.
Sci Adv ; 4(6): eaar5598, 2018 06.
Article em En | MEDLINE | ID: mdl-29928692
Men are much more likely than women to develop bladder cancer (BCa), but the underlying cause of this gender disparity remains poorly defined. Using sex-reversed mice, we show that the sex chromosome complement is an independent cause and, moreover, amplifies the biasing effects of sex hormones. We also show that the X-linked lysine demethylase 6A (KDM6A) is a sexually dimorphic gene. Wild-type but not catalytically dead KDM6A confers sustained tumor suppressor activity in vitro. Knockout of mouse Kdm6a reduces expression of Cdkn1a and Perp, canonical gene targets of the tumor suppressor p53. Consistently, loss of Kdm6a increases BCa risk in female mice, and mutations or reduced expression of human KDM6A predicts poor prognosis of female BCa patients. Collectively, the study reveals that the X chromosome protects against BCa among females via a KDM6A-dependent epigenetic mechanism and further suggests that KDM6A is a prototypical sex-biasing tumor suppressor with both demethylase-dependent and demethylase-independent activities.
Assuntos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Cromossomo X / Neoplasias da Bexiga Urinária / Regulação Neoplásica da Expressão Gênica / Predisposição Genética para Doença / Epigênese Genética / Histona Desmetilases Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Sci Adv Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Cromossomo X / Neoplasias da Bexiga Urinária / Regulação Neoplásica da Expressão Gênica / Predisposição Genética para Doença / Epigênese Genética / Histona Desmetilases Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Sci Adv Ano de publicação: 2018 Tipo de documento: Article País de afiliação: Estados Unidos