TCTP participate in hepatic metabolism with regulate the gene expression involved in insulin resistance

The translationally controlled tumor protein (TCTP) has various cellular functions and molecular interactions, many related to its growth promoting and antiapoptotic properties. Recently, TCTP highly increased expression in high-fat diet-fed mice with insulin-resistant states. Despite TCTP is a multifunction protein, but its role in liver metabolism is still unknown. Here, we investigated the function and mechanism of TCTP in HepG2 cells. Knock-down the TCTP regulated 287 differentially expressed genes and these genes are highly associated with the cellular apoptosis and stress, NF-kB, Glycolysis/Gluconeogenesis, insulin resistance. TCTP deletion selectively downregulated the expression of PCK1 and G6PC in glucose metabolism. Furthermore, TCTP regulated the alternative splicing of genes enriched in phospholipid biosynthetic process, and glycerophospholipid metabolism. Our results implied that TCTP regulates liver cell transcriptome at both the transcriptional and alternative splicing levels. The TCTP regulatory network predicts the biological functions of TCTP in glycometabolism and lipid metabolism, which may be associated with liver metabolism and induces fatty liver disease through enhanced insulin resistant signaling. transcrptional analysis of TCTP knock-down and control in HepG2 cells