Transgenic expression of the RNA binding protein IMP2 stabilizes miRNA targets in murine microsteatosis

Adult expression of IMP2 is often associated with several types of cancer. The RNA binding protein IMP2 bindsand stabilizes the IGF2 mRNA as well as hundreds of other transcripts during development. Here we analyzetransgenic overexpression of IMP2 in mouse livers, which has been shown to induce a steatosis-like phenotype.Our data shows drastic up-regulation of several marker genes for hepatocellular carcinoma (HCC) and upregulationof two miRNAs frequently overexpressed in HCC, miR438-3p and 151-5p, supporting the enhancedrisk of IMP2 livers to develop HCC. To characterize the impact of miRNAs to their targets, integrative analysis oftranscriptome- and miRNAome-dynamics in combination with IMP2 target prediction was carried out. Ouranalyses show that targets of expressed miRNAs become accumulated in the case that these transcripts havepositive IMP2 binding prediction. Therefore, our data indicates that overexpression of IMP2 alters theregulatory capacity of many miRNAs and we conclude that IMP2 competes with miRNAs for binding sites onthousands of transcripts. As a result, our data implicates that oncogenic overexpression of IMP2 has distincteffects to the regulatory capacity of miRNAs with yet unknown consequences for translational efficiency.