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miR-122 removal in the liver activates imprinted microRNAs and enables more effective microRNA-mediated gene repression

Author

Listed:
  • Paul N. Valdmanis

    (Stanford University
    Stanford University
    University of Washington School of Medicine)

  • Hak Kyun Kim

    (Stanford University
    Stanford University)

  • Kirk Chu

    (Stanford University
    Stanford University)

  • Feijie Zhang

    (Stanford University
    Stanford University)

  • Jianpeng Xu

    (Stanford University
    Stanford University)

  • Elizabeth M. Munding

    (Stanford University
    Stanford University)

  • Jia Shen

    (Stanford University
    Stanford University)

  • Mark A. Kay

    (Stanford University
    Stanford University)

Abstract

miR-122 is a highly expressed liver microRNA that is activated perinatally and aids in regulating cholesterol metabolism and promoting terminal differentiation of hepatocytes. Disrupting expression of miR-122 can re-activate embryo-expressed adult-silenced genes, ultimately leading to the development of hepatocellular carcinoma (HCC). Here we interrogate the liver transcriptome at various time points after genomic excision of miR-122 to determine the cellular consequences leading to oncogenesis. Loss of miR-122 leads to specific and progressive increases in expression of imprinted clusters of microRNAs and mRNA transcripts at the Igf2 and Dlk1-Dio3 loci that could be curbed by re-introduction of exogenous miR-122. mRNA targets of other abundant hepatic microRNAs are functionally repressed leading to widespread hepatic transcriptional de-regulation. Together, this reveals a transcriptomic framework for the hepatic response to loss of miR-122 and the outcome on other microRNAs and their cognate gene targets.

Suggested Citation

  • Paul N. Valdmanis & Hak Kyun Kim & Kirk Chu & Feijie Zhang & Jianpeng Xu & Elizabeth M. Munding & Jia Shen & Mark A. Kay, 2018. "miR-122 removal in the liver activates imprinted microRNAs and enables more effective microRNA-mediated gene repression," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07786-7
    DOI: 10.1038/s41467-018-07786-7
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