GSE111805
Small and large RNA sequencing of mouse livers during development and after miR-122 exicision
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. Overall design: RNA sequencing of 14 liver samples of mice with LoxP sites surrounding mature miR-122.  Triplicate of uninjected mice and mice harvested 21, and 45 days after receiving AAV-Cre and one mouse each 100 or 200 days after Cre.  Triplicate liver samples of additional germline miR-122 knockout mice.  Small RNA sequencing of the same liver samples along with additional time points after Cre removal of miR-122.  Small RNA sequencing of livers of wildtype 129Sv/J mice at various stages of embryo and post-natal development.