FASN Promotes Invasion And Migration In HCC By Interacting With STAT3

BACKGROUND: Hepatocellular carcinoma(HCC)is a very common malignant tumor in the world,and it is also a very common primary malignant tumor of the liver.The possibility of metastasis of common hepatocellular carcinoma is high in the world,so this is one of the reasons for the limited choice of treatment for common hepatocellular carcinoma.Fatty acid synthase(FASN)is a very important and well studied metabolic enzyme in human cells.FASN is involved in many steps of tumorigenesis and progression,including invasion and migration of tumors,proliferation and survival of tumour cells.METHODS: In this article,immunohistochemical experiments were used to confirm the validity of the previous experiments;Transwell and scratch experiments were used to further confirm the biological effects of high expression of FASN on the progression of hepatocellular carcinoma in hepatocellular carcinoma cell lines;secondly,immunoprecipitation experiments were carried out on hepatocellular carcinoma cell lines treated with FASN siRNA and control siRNA to obtain the protein.Samples were identified by relative and absolute quantification(ITRAQ),a common proteomic method,using isobaric labels.Then the results of ITRAQ were verified by immunofluorescence analysis and co-immunoprecipitation experiments.Finally,Western blotting was used to further explore the specific mechanism of FASN in hepatocellular carcinoma.RESULTS: 1.Immunohistochemical experiments confirmed that the expression of FASN in hepatocellular carcinoma was significantly higher than that in normal hepatocellular carcinoma tissues adjacent to hepatocellular carcinoma.2.Transwell experiment confirmed that knocking down FASN in hepatocellular carcinoma cell lines could inhibit the invasion of hepatocellular carcinoma cell lines.The scratch experiment also confirmed that knocking down FASN in hepatocellular carcinoma cell lines could inhibit the migration of hepatocellular carcinoma cell lines.3.ITRAQ experiment screened out a variety of interacting prote We selected STAT3(signal transduction and activator of transcription 3)for subsequent experiments.4.Immunofluorescence analysis and co-immunoprecipitation confirmed the accuracy of ITRAQ results,that is,both methods confirmed the interaction between FASN and STAT3.5.Western blotting confirmed that when we knocked down FASN in hepatocellular carcinoma cell lines,the expression of STAT3 had no statistical significance,while phosphorylated STAT3 and its downstream acting proteins MMP-9 and MMP-2 had a downward trend.CONCLUSION: Our results suggest that FASN may affect the STAT3 signal pathway and the expression of MMP-9 and MMP-2 by interacting with STAT3 in hepatocellular carcinoma,thus promoting the progression of hepatocellular carcinoma.