LncRNA HAND2-AS1 promotes liver cancer stem cell self-renewal via BMP signaling.
EMBO J
; 38(17): e101110, 2019 09 02.
Article
em En
| MEDLINE
| ID: mdl-31334575
ABSTRACT
Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal maintenance is poorly understood. Here, we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 and its mouse ortholog lncHand2 display a high level of conservation. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanistically, HAND2-AS1 recruits the INO80 chromatin-remodeling complex to the promoter of BMPR1A, thereby inducing its expression and leading to the activation of BMP signaling. Importantly, interfering with expression of HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs has synergistic anti-tumorigenic effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, offering a potential new target for HCC therapy.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Transdução de Sinais
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Carcinoma Hepatocelular
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RNA Longo não Codificante
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Neoplasias Hepáticas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
EMBO J
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China