Hepatic Loss of Borealin Impairs Postnatal Liver Development, Regeneration, and Hepatocarcinogenesis
Hepatic Loss of Borealin Impairs Postnatal Liver Development, Regeneration, and Hepatocarcinogenesis
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肝脏中 Borealin 的丢失会损害产后肝脏的发育、再生和肝癌的发生
DOI：
10.1074/jbc.m116.736173
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发表时间：
2016-09-30
影响因子：
4.8
通讯作者：
Hui, Lijian
中科院分区：
文献类型：
--
作者：
Li, Lu;Li, Dan;Hui, Lijian
Borealin是染色体乘客复合体的一员，在有丝分裂过程中在着丝粒和中央纺锤体上起着关键的调节作用。Borealin的缺失导致细胞增殖缺陷和早期胚胎死亡。Borealin在哺乳动物出生后发育、组织稳态和肿瘤发生中的体内功能仍然是难以捉摸的。我们使用携带条件性Borealin等位基因的小鼠，具体分析了Borealin在调节出生后肝脏发育、损伤诱导的肝再生和肝癌发生中的作用。围产期Borealin的丢失会导致肝细胞基因组倍性增加和细胞大小增大，这可能是由于有丝分裂中染色体乘客复合体的功能受损。在3，5-二乙氧羰基-1，4-二氢可力丁饮食诱导的肝损伤中，Borealin缺失也显示Sox 9（+）HNF 4 α（+）祖细胞样细胞在肝再生中的扩增减弱。此外，Delta N90-β-连环蛋白和c-Met诱导的肝癌发生发展在很大程度上受到Borealin缺失的阻碍。这些发现表明，Borealin在肝脏发育，再生和肿瘤发生中起着关键作用，并表明Borealin可能是相关肝脏疾病的潜在靶点。
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(+)HNF4 alpha(+) progenitor-like cells in liver regeneration during 3,5-diethoxycarbonyl-1,4-dihydrocollidine diet-inducedliverinjury. Moreover, Delta N90-beta-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.