Hepatic Loss of Borealin Impairs Postnatal Liver Development, Regeneration, and Hepatocarcinogenesis.
J Biol Chem
; 291(40): 21137-21147, 2016 Sep 30.
Article
em En
| MEDLINE
| ID: mdl-27542413
ABSTRACT
Borealin, a member of the chromosomal passenger complex, plays a key regulatory role at centromeres and the central spindle during mitosis. Loss of Borealin leads to defective cell proliferation and early embryonic lethality. The in vivo functions of Borealin in mammalian postnatal development, tissue homeostasis, and tumorigenesis remain elusive. We specifically analyzed the role of Borealin in regulating postnatal liver development, damage-induced liver regeneration, and liver carcinogenesis using mice carrying conditional Borealin alleles. Perinatal loss of Borealin caused increased genome ploidy and enlarged cell size in hepatocytes, likely due to the impaired function of the chromosomal passenger complex in mitosis. Borealin deletion also showed attenuated expansion of Sox9+HNF4α+ progenitor-like cells in liver regeneration during 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-induced liver injury. Moreover, ΔN90-ß-Catenin and c-Met-induced hepatocarcinogenesis development was largely impeded by Borealin deletion. These findings indicate that Borealin plays a key role in liver development, regeneration, and tumorigenesis and suggests that Borealin could be a potential target for related liver diseases.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Proteínas Cromossômicas não Histona
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Proteínas de Ciclo Celular
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Hepatócitos
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Fígado
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Neoplasias Hepáticas
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Regeneração Hepática
Limite:
Animals
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2016
Tipo de documento:
Article