let-7 Modulates Chromatin Configuration and Target Gene Repression through Regulation of the ARID3B Complex.
Cell Rep
; 14(3): 520-533, 2016 Jan 26.
Article
em En
| MEDLINE
| ID: mdl-26776511
ABSTRACT
Let-7 is crucial for both stem cell differentiation and tumor suppression. Here, we demonstrate a chromatin-dependent mechanism of let-7 in regulating target gene expression in cancer cells. Let-7 directly represses the expression of AT-rich interacting domain 3B (ARID3B), ARID3A, and importin-9. In the absence of let-7, importin-9 facilitates the nuclear import of ARID3A, which then forms a complex with ARID3B. The nuclear ARID3B complex recruits histone demethylase 4C to reduce histone 3 lysine 9 trimethylation and promotes the transcription of stemness factors. Functionally, expression of ARID3B is critical for the tumor initiation in let-7-depleted cancer cells. An inverse association between let-7 and ARID3A/ARID3B and prognostic significance is demonstrated in head and neck cancer patients. These results highlight a chromatin-dependent mechanism where let-7 regulates cancer stemness through ARID3B.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Proteínas de Ligação a DNA
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article