RNAseq analysis reveals transcriptome changes associated with the progression of non-alcoholic liver disease in livers fromEfcab4bknockout mice

Abstract

ABSTRACTEFCAB4Bis an evolutionarily conserved protein that encodes for the Rab GTPase Rab46, and the CRAC channel modulator, CRACR2A. Previous genome wide association studies have demonstrated the association ofEFCAB4Bvariants in the progression of non-alcoholic liver disease (NAFLD). In this study we show that mice with global depletion ofEfcab4b-/-have significantly larger livers than their wild-type (WT) counterparts. We performed RNA-sequencing (RNA-seq) analysis of liver tissues to investigate differential global gene expression amongEfcab4b-/-and WT mice. Of the 69 differentially expressed genes (DEGs), analyses of biological processes found significant enrichment in liver and bile development, with 6 genes (Pck1, Aacs, Onecut1, E2f8, Xbp1,andHes1) involved in both processes. Specific consideration of possible roles of DEGs or their products in NAFLD progression to (NASH) and hepatocarcinoma (HCC), demonstrated DEGs in the livers ofEfcab4b-/-mice had roles in molecular pathways including lipid metabolism, inflammation, ER stress and fibrosis. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated withEFCAB4B.