miR-122 removal in the liver activates imprinted microRNAs and enables more effective microRNA-mediated gene repression.
Nat Commun, 2018/12/14;9(1):5321.
Valdmanis PN[1, 2, 3], Kim HK[4, 5], Chu K[4, 5], Zhang F[4, 5], Xu J[4, 5], Munding EM[4, 5], Shen J[4, 5], Kay MA[6, 7]
Affiliations
PMID: 30552326DOI: 10.1038/s41467-018-07786-7
Impact factor: 17.694
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.
MeSH terms
Animals; Calcium-Binding Proteins; Carcinogenesis; Carcinoma, Hepatocellular; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; HEK293 Cells; Hepatocytes; Humans; Insulin-Like Growth Factor II; Intercellular Signaling Peptides and Proteins; Iodide Peroxidase; Liver; Liver Neoplasms; Membrane Proteins; Mice; Mice, Knockout; MicroRNAs; RNA, Messenger; Transcriptome
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