LncAPC drives Wnt/ß-catenin activation and liver TIC self-renewal through EZH2 mediated APC transcriptional inhibition.
Mol Carcinog
; 57(3): 408-418, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-29144570
ABSTRACT
Liver tumor initiating cells (TICs), a small subset cells in tumor bulk, are responsible for liver tumor initiation, metastasis, and relapse. However, the regulatory mechanism of liver TICs remains largely unknown. Here we found a long noncoding RNA lncAPC, locating near from APC locus, was highly expressed in liver cancer and liver TICs. LncAPC was required for liver TIC self-renewal. Silencing and overexpressing lncAPC showed impaired and enhanced sphere formation capacity of liver TICs, respectively. By recruiting EZH2 to APC promoter, LncAPC inhibits APC transcription and thus drives the activation of Wnt/ß-catenin signaling. Attenuate binding between EZH2 and APC promoter was observed upon lncAPC knockdown. What is more, lncAPC-EZH2-APC axis can be targeted to eliminate liver TICs. Altogether, LncAPC promotes liver TIC self-renewal through EZH2-dependent APC transcriptional inhibition.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Regulação Neoplásica da Expressão Gênica
/
Proteína da Polipose Adenomatosa do Colo
/
RNA Longo não Codificante
/
Proteína Potenciadora do Homólogo 2 de Zeste
/
Neoplasias Hepáticas
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Mol Carcinog
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China