title: Hepatic Loss of Borealin Impairs Postnatal Liver Development, Regeneration, and Hepatocarcinogenesis.
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-β-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.
authors.affiliation: From the State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai and the University of Chinese Academy of Sciences, and.
authors.forename: Lu
authors.initials: L
authors.lastname: Li
authors.affiliation: From the State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai and lidan@sibcb.ac.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: the Department of Pathology, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Tian
authors.affiliation: From the State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai and.
authors.forename: Jin
authors.initials: J
authors.lastname: Cen
authors.affiliation: From the State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai and.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Chen
authors.affiliation: the Department of Pathology, Zhongshan Hospital, Fudan University, Fenglin Road 180, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: From the State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai and ljhui@sibcb.ac.cn.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000172:deficiency* / Q000378:metabolism; D048429:Cell Size; D002868:Chromosomal Proteins, Non-Histone / Q000172:deficiency* / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration; D051379:Mice; D008817:Mice, Mutant Strains; D011003:Ploidies; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: C530978:CDCA8 protein, mouse; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D051557:Hepatocyte Nuclear Factor 4; C496593:Hnf4a protein, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D019859:Proto-Oncogene Proteins c-met
keywords: Borealin; cell cycle; hepatocellular carcinoma; liver cancer; liver development; liver injury; liver progenitor-like cell; stem cells