Partial Hepatectomy Induced Long Noncoding RNA Inhibits Hepatocyte Proliferation during Liver Regeneration

• Published in: PloS one Vol. 10; no. 7; p. e0132798
• Main Authors: Huang, Lulu, Damle, Sagar S, Booten, Sheri, Singh, Priyam, Sabripour, Mahyar, Hsu, Jeff, Jo, Minji, Katz, Melanie, Watt, Andy, Hart, Christopher E, Freier, Susan M, Monia, Brett P, Guo, Shuling
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 24.07.2015; Public Library of Science (PLoS)
• Subjects: Animals; Antisense oligonucleotides; Bioinformatics; Biological activity; Cell adhesion & migration; Cell cycle; Cell growth; Cell proliferation; Cell Proliferation - genetics; Cells, Cultured; Deoxyribonucleic acid; Depletion; DNA; DNA microarrays; DNA-directed DNA polymerase; Feedback loops; Gene expression; Gene Expression Profiling; Genomes; Genomics; Hepatectomy; Hepatocytes - physiology; Liver; Liver Regeneration - genetics; Male; Mice; Mice, Inbred C57BL; Microarray Analysis; Negative feedback; Oligonucleotides; Pharmaceuticals; Post-transcription; Proteins; R&D; Regeneration; Research & development; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - physiology; Stem cells; Transcription factors; Up-Regulation - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0132798

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.