Dissecting AP-1 complexity in hepatic health and disease using Genetically Modified Mice

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death with limited, while treatment options. Thus, a better understanding of the molecular pathways involved in HCC development has become a priority to guide future therapies. While previous studies implicated the AP-1 (Fos/Jun) transcription factor family members c-Fos and c-Jun in HCC formation, the contribution of Fos-related antigens 1 and 2 (Fra-1/2) is unknown. Here we analyse the transcriptional consequences of hepatocyte-restricted expression of Fra-1 and Fra-2 proteins in the liver of young adult mice during 2 months by bulk RNA-seq. RNA from murine (adult males, C57BL/6) liver samples was sequenced 2 months after transgene induction from two closely related strains Fra1hep (in 3 controls and 3 mutants, littermates) and Fra-2hep (in 3 controls and 3 mutants, littermates). Transgene expression in the mutants was always started at weaning (3 weeks of age) by doxyciclin removal. Controls were littermates kept in the same cage and that received the same treatment. Comparative expression profiling was conducted across genotype (mutants compared to controls) and also compared to control and mutants from an already published strain that were kept in identical conditions (GSE261005). Grant ID: 741888 (ERC AdG 2016) Grant title: CSI-Fun Funding source: European Research Council Grantee name: Erwin F.Wagner Grant ID: 859860 (ITN 2019) Grant title: CANCERPREV Funding source: H2020 - MSCA Grantee name: Erwin F. Wagner