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 unde...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 b-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 b-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.展开更多
基金We would like to thank Dr.Tong-Chuan He(University of Chicago,USA)for providing the AdEasy system.This study was supported by research grants from China National Natural Science Foundation(grant nos.81602417 to KW,and 81872270 and 81572683 to NT),the Major National S&T program(2017ZX10202203-004 to NT)Natural Science Foundation Project of CQ CSTC(grant no.cstc2018jcyjAX0254 to NT)The Program for Innovation Team of Higher Education in Chongqing(grant no.CXTDX201601015).
文摘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 b-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 b-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.
