title: Partial Hepatectomy Induced Long Noncoding RNA Inhibits Hepatocyte Proliferation during Liver Regeneration.
abstract: Liver regeneration after partial hepatectomy (PHx) is a complex and well-orchestrated biological process in which synchronized cell proliferation is induced in response to the loss of liver mass. To define long noncoding RNAs (lncRNAs) that participate in the regulation of liver regeneration, we performed microarray analysis and identified more than 400 lncRNAs exhibiting significantly altered expression. Of these, one lncRNA, LncPHx2 (Long noncoding RNA induced by PHx 2), was highly upregulated during liver regeneration. Depletion of LncPHx2 during liver regeneration using antisense oligonucleotides led to a transient increase in hepatocyte proliferation and more rapid liver regeneration. Gene expression analysis showed that LncPHx2 depletion resulted in upregulation of mRNAs encoding proteins known to promote cell proliferation, including MCM components, DNA polymerases, histone proteins, and transcription factors. LncPHx2 interacts with the mRNAs of MCM components, making it a candidate to regulate the expression of MCMs and other genes post-transcriptionally. Collectively, our data demonstrate that LncPHx2 is a key lncRNA that participates in a negative feedback loop modulating hepatocyte proliferation through RNA-RNA interactions.
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Lulu
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Damle
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Sheri
authors.initials: S
authors.lastname: Booten
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Priyam
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Mahyar
authors.initials: M
authors.lastname: Sabripour
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Jeff
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Minji
authors.initials: M
authors.lastname: Jo
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Melanie
authors.initials: M
authors.lastname: Katz
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Andy
authors.initials: A
authors.lastname: Watt
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Hart
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Freier
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Brett P
authors.initials: BP
authors.lastname: Monia
authors.affiliation: Department of Antisense Drug Discovery, Isis Pharmaceuticals Inc., Carlsbad, CA, 92010, United States of America.
authors.forename: Shuling
authors.initials: S
authors.lastname: Guo
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000235:genetics*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D006498:Hepatectomy; D022781:Hepatocytes / Q000502:physiology*; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics
chemical_list: D062085:RNA, Long Noncoding