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).   We interrogated 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 led 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 became 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. SOURCE: Paul Valdmanis (paulv@stanford.edu) - Mark Kay Stanford University

Pluto Bioinformatics

GSE111805: Small and large RNA sequencing of mouse livers during development and after miR-122 exicision