Phosphoenolpyruvate carboxykinase 1 (PCK1)

a step limiting enzyme of gluconeogenesis

is downregulated in hepatocellular carcinoma (HCC). Overexpression of PCK1 has been shown to suppress hepatoma cell growth

but the underlying mechanism remains unclear. We used recombinant adenovirus overexpressing PCK1 or GFP in Huh7 cells

and the differentially expressed genes (DEGs) were identified by RNA-Seq. 180 were upregulated by PCK1 overexpression

whereas 316 were downregulated. Pathway analysis illustrated that PCK1 was closely correlated with Wnt signaling pathway and TGF-beta signaling pathway. Hence

Wnt signaling pathway and its downstream component

FZD2

FZD6

FZD7 and β-catenin were confirmed by qRT-PCR and Western blot. In vivo we also observed that PCK1 had restrained tumor growth as a result of decreasing expression of β-catenin. Whole-transcriptomic profile analysis discovered that overexpression of PCK1 downregulates several oncogenic signaling pathways in HCC

providing potential therapeutic targets for improving HCC therapy.