title: Long noncoding RNAs associated with liver regeneration 1 accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-catenin signaling.
abstract: In recent years, long noncoding RNAs (lncRNAs) have been investigated as a new class of regulators of biological function. A recent study reported that lncRNAs control cell proliferation in hepatocellular carcinoma (HCC). However, the role of lncRNAs in liver regeneration and the overall mechanisms remain largely unknown. To address this issue, we carried out a genome-wide lncRNA microarray analysis during liver regeneration in mice after 2/3 partial hepatectomy (PH) at various timepoints. The results revealed differential expression of a subset of lncRNAs, notably a specific differentially expressed lncRNA associated with Wnt/β-catenin signaling during liver regeneration (an lncRNA associated with liver regeneration, termed lncRNA-LALR1). The functions of lncRNA-LALR1 were assessed by silencing and overexpressing this lncRNA in vitro and in vivo. We found that lncRNA-LALR1 enhanced hepatocyte proliferation by promoting progression of the cell cycle in vitro. Furthermore, we showed that lncRNA-LALR1 accelerated mouse hepatocyte proliferation and cell cycle progression during liver regeneration in vivo. Mechanistically, we discovered that lncRNA-LALR1 facilitated cyclin D1 expression through activation of Wnt/β-catenin signaling by way of suppression of Axin1. In addition, lncRNA-LALR1 inhibited the expression of Axin1 mainly by recruiting CTCF to the AXIN1 promoter region. We also identified a human ortholog RNA of lncRNA-LALR1 (lncRNA-hLALR1) and found that it was expressed in human liver tissues.
  
  
  CONCLUSIONS
  lncRNA-LALR1 promotes cell cycle progression and accelerates hepatocyte proliferation during liver regeneration by activating Wnt/β-catenin signaling. Pharmacological intervention targeting lncRNA-LALR1 may be therapeutically beneficial in liver failure and liver transplantation by inducing liver regeneration.
authors.affiliation: Department of Medical Genetics, Second Military Medical University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.forename: Fu
authors.initials: F
authors.lastname: Yang
authors.forename: Ji-hang
authors.initials: JH
authors.lastname: Yuan
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Hai-shan
authors.initials: HS
authors.lastname: Bi
authors.forename: Chuan-chuan
authors.initials: CC
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Shu-han
authors.initials: SH
authors.lastname: Sun
mesh_terms: D051700:Activating Transcription Factor 3 / Q000502:physiology*; D000328:Adult; D000818:Animals; D060466:Axin Protein / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D049109:Cell Proliferation; D005260:Female; D006498:Hepatectomy; D022781:Hepatocytes / Q000473:pathology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000473:pathology / Q000502:physiology / Q000601:surgery; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: D051700:Activating Transcription Factor 3; D060466:Axin Protein; C555452:Axin1 protein, mouse; D062085:RNA, Long Noncoding; D051153:Wnt Proteins; D051176:beta Catenin; C068616:liver regeneration factor 1