FXR1 regulates transcription and is required for growth of human cancer cells with TP53/FXR2 homozygous deletion.
Elife
; 62017 08 02.
Article
em En
| MEDLINE
| ID: mdl-28767039
ABSTRACT
Tumor suppressor p53 prevents cell transformation by inducing apoptosis and other responses. Homozygous TP53 deletion occurs in various types of human cancers for which no therapeutic strategies have yet been reported. TCGA database analysis shows that the TP53 homozygous deletion locus mostly exhibits co-deletion of the neighboring gene FXR2, which belongs to the Fragile X gene family. Here, we demonstrate that inhibition of the remaining family member FXR1 selectively blocks cell proliferation in human cancer cells containing homozygous deletion of both TP53 and FXR2 in a collateral lethality manner. Mechanistically, in addition to its RNA-binding function, FXR1 recruits transcription factor STAT1 or STAT3 to gene promoters at the chromatin interface and regulates transcription thus, at least partially, mediating cell proliferation. Our study anticipates that inhibition of FXR1 is a potential therapeutic approach to targeting human cancers harboring TP53 homozygous deletion.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
/
Proteína Supressora de Tumor p53
/
Proteínas de Ligação a RNA
/
Deleção de Sequência
/
Homozigoto
/
Neoplasias
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article