The Function And Mechanism Of FABP4 In The Development And Progression Of Hepatocellular Carcinoma

Background & ObjectiveHepatocellular carcinoma(HCC)is one of the most common malignant tumors,the incidence of liver cancer ranks fifth,and the mortality is third in the world.Abundant evidences showed that the occurrence of HCC was associated with multiple gene mutations,but the pathogenesis was still unclear.Tumor related genes play an important role in the process of hepatocarcinogenesis.The corresponding targeted therapy has been paid enough attention,especially for advanced HCC patients,according to the different gene mutations with the development of modern medical precision,.Fatty acid binding protein 4(FABP4)is a member of the fatty acid binding protein family,which is mainly expressed in macrophages and adipose cells,binding to specific fatty acid receptor,and plays an important role in energy metabolism of tumor cells.It was reported that FABP4 was closely related to the occurrence and development of various tumors and affected these biological function.However,its function and mechanism in HCC is still unknown.Methods1.To collect 64 pairs of HCC and the corresponding adjacent tissues,of which,50 pairs for Real-time PCR test,the other 14 pairs for Western Blot test,to detect the m RNA level and protein level of FABP4 respectively.The expression of FABP4 was detected by immunohistochemistry using a tissue microarray which include 175 pairs of HCC tissues and corresponding adjacent tissue;2.Analyzing of the relationship between FABP4 and clinicopathological features of HCC patients with ?~2 test and t test;3.Using Kaplan-Meier to analyze the relationship between FABP4 expression level and prognosis(including DFS and OS)of HCC patients,then to be verified by Log-rank test;4.To analyze whether the expression of FABP4 in HCC tissues was an independent prognostic factor of HCC patients using COX proportional regression model;5.P23-FABP4 plasmid containing the FABP4 open reading frame and a p LKO.1-puro plasmid expressing FABP4 si RNA were constructed.These two plasmids were transfected into HCC cells and stable expressing FABP4(YY-8103,7404)or FABP4 sh RNA(MHCC-H,MHCC-L),both which were selected using puro or flow cytometry,respectively;6.The proliferation of the HCC cells was detected by MTT and crystal violet assaay,and the migration ability of the cells was detected by Boyden Chamber assay;7.The proliferation of HCC cells in vivo was detected by subcutaneous tumor in nude mice;8.The protein was extracted and the expression of the FABP4 and some common signal pathwayswas were analyzed by Western Blot.Results1.The expression of FABP4 in HCC tissues was significantly lower than that in adjacent tissues,and there was a significant correlation between FABP4 expression and clinicopathological features(tumor diameter and MVI);2.Patients with low FABP4 expression were always with a poor DFS and OS,and FABP4 could be used as an independent indicator to determine the prognosis of HCC patients;3.The over/low expression of FABP4 can significantly inhibit the proliferation and migration of HCC cells;4.In vivo,we found that over expression of FABP4 could inhibit the proliferation of subcutaneous tumor;5.FABP4 can inhibit the proliferation of hepatoma cells by inhibiting the phosphorylation of STAT3 and inhibit the migration ability by inhibiting the expression of snail protein;ConclusionsThe expression of FABP4 in HCC tissues was significantly lower than that in adjacent tissues,and FABP4 could be used as an independent risk factor for DFS and OS of HCC patients.High expression of FABP4 can inhibit the proliferation and migration of HCC cell lines,which may be related to the down regulation of snail and p-STAT3.These results indicate that FABP4 may serve as a potential therapeutic target for HCC.