Effects Of HDGF On The De Novo Lipogenesis And Proliferation Of Hepatocellular Cancer Cells

Background and ObjectiveAbnormal tumor metabolism is an important feature of the tumor.De novo lipogenesis is highly activated in hepatocellular carcinoma as other types of malignancies.SREBP1 a,a member of the sterol regulatory element binding protein families,is a key transcription factor that regulates de novo lipogenesis,directly regulating genes involved in key enzymes of de novo lipogenesis(such as FASN,SCD)and affecting cell growth.Hepatoma-derived growth factor is a growth factor and nuclear transcription factor playing important roles in promoting proliferation in a variety of tumor cells,and closely related to the poor prognosis of the tumor.In this study,we investigated the potential molecular mechanism of the effects of HDGF on the de novo lipogenesis and the biological effects of hepatocellular cancer cells through a series of experiments in vitro and in vivo.MethodReal-time fluorescence quantitative PCR was used to detect the m RNA expression of genes.Triglyceride assay,cholesterol assay and Oil red O staining indirectly and directly reflected intracellular lipid metabolism level,respectively.According to the literature,Pro24,an important site of its functional structure,was determined.GST-pull down assay and Western blotting were used to verify the binding of proteins.Chromatin immunoblotting was used to detect the DNA fragment binding to the target protein.Cell counting kit 8 assay,soft agar colony formation assay and xenograft study reflected the proliferation of tumor cells in vitro and in vivo.Immunohistochemical staining assay was used to analyze the expression of specific antigen in tissues.ResultThe results of real-time fluorescence quantitative PCR,triglyceride assay,cholesterol assay and Oil red O staining confirmed that down regulation of HDGF suppressed SREBP1 mediated regulation of lipid metabolism genes.GST-Pulldown technology,Co-IP and Ch IP further vertify that P24 A exerts its transcriptional repression not only by binding to transcriptional repressor C-terminal binding protein(Ct BP),also inhibiting the regulation of downstream transcription factors by SREBP1,thereby inhibiting de novo lipiogenesis and the proliferation of hepatocellular cancer cells in vitro and in vivo.Immunohistochemistry detects that nuclear HDGF was a poor prognostic factor for HCC.The expression of nuclear HDGF and SREBP1 is correlated.The co-expression nuclear HDGF and SREBP1 predicts poor prognosis of HCC.ConclusionHDGF is a poor prognostic factor for HCC.Both HDGF silencing and changes in the structure of HDGF inhibit de novo lipogenesis and proliferation of hepatocellular cancer cells.The expression of nuclear HDGF and SREBP1 is correlated.The co-expression nuclear HDGF and SREBP1 predicts poor prognosis of HCC.