Expression Of PRMT7 In Hepatocellular Carcinoma And Its Effect On Tumor Biological Behavior

Background:Hepatocellular carcinoma(HCC)is one of the most common and fatal malignancies.It has insidious onset,rapid development and high degree of malignancy.There is no obvious discomfort in the early stage of the HCC,and it has developed to the middle or late stage when the diagnosis is made.Protein arginine methyltransferase 7(PRMT7)is a monomethylated PRMT,which plays an important role in regulating DNA damage repair,stem cell pluripotency and tumorigenesis.The purpose of this study was to investigate the expression of PRMT7 in HCC and its relationship with poor prognosis,as well as to explore the biological effect and molecular mechanism of PRMT7 in the malignant progression of HCC,so as to find a molecular marker and drug target related to the early diagnosis of HCC.Method:1.Specimens including 81 cases with HCC and pericarcinomatous tissue in 2015 and the clinicopathological parameters of each case were collected at Qi Lu Hospital of Shandong University.The differences of PRMT7 expression in HCC tissues and pericarcinomatous tissue were detected by immunohistochemistry,and then the correlation between PRMT7 expression with various clinicopathological parameters was analyzed by SPSS.2.Log-rank test was used for statistical analysis of survival of successful follow-up HCC patients,and kaplan-meier method was used to draw survival curves for these cases.Meanwhile,univariate and multivariate COX regression analysis was performed on these patients using COX regression model to explore independent risk factors related to the prognosis of HCC.3.Using qRT-PCR technology to detect the expression level of PRMT7 in normal liver cell line L02 and three liver cancer cell lines HepG2,BEL7402,SMMC-7721.4.Changes in proliferation,migration,invasion and apoptosis of HepG2 cell lines were detected after overexpression and knockdown of PRMT7,respectively.5.The relationship between PRMT7 and proliferation,EMT-related proteins and signaling pathways was detected by western blot.Results:1.PRMT7 is low expression in HCC tissues and high expression in pericarcinomatous tissues,and the expression pattern is cytoplasmic expression.PRMT7 low expression was correlated with tumor diameter>5cm,AST>40 U/L,ALT>40 U/L,LDH>250 U/L.2.Survival analysis showed that low expression of PRMT7 and AFP>10Ong/ml were associated with HCC poor prognosis.COX regression model analysis showed that low PRMT7 expression is an independent risk factor for predicting the prognosis of patients with HCC.Although AFP>100ng/ml is a factor of shortened survival,it is not an independent risk factor for predicting the prognosis of HCC patients.3.The expression level of PRMT7 in normal liver cell line L02 is higher than that of three HCC cell lines HepG2,BEL7402 and SMMC-7721,which is consistent with histological results.4.In HepG2 cell line,overexpression of PRMT7 can decrease cell proliferation,migration and invasion ability and increase apoptosis,and knockdown of PRMT7 can increase cell proliferation,migration and invasion and decrease cell apoptosis.5.In HepG2 cell line,overexpression of PRMT7 can decrease the expression of vimentin,ZEB2,ki67 and p-Catenin,and inhibit the P13K/AKT/mTOR signaling pathway.Conclusion:PRMT7 is low expression in HCC and high expression in pericarcinomatous tissues.Low expression of PRMY7 enables HCC cells to increase proliferation,migration and invasion ability and inhibit cell apoptosis,which may be related to the increased expression of ki67,?-Catenin,vimentin,ZEB2 and activation of PI3K/AKT/mTOR signaling pathway.