ZNF436 Inhibit Hepatocellular Carcinoma Progression By Combining With TRIM28

Background and aimsKRAB-containing Zinc finger protein,whose N terminal contains Kruppel-associated box(KRAB)domain,functions as repressors and/or activators to control transcriptional regulation of gene expression in various of diseases,e.g.in the Wilms’ tumor and breast cancer.ZNF436 is a member of the zinc finger transcription factor family.Despite recent study show that it may act as a negative regulator in gene transcription mediated by MAPK signaling pathways,the potential role of ZNF436 and underlying signaling network association with HCC remains largely uncertain.Tripartite motif-containing proteins 28 functions as a corepressor of Kruppel-associated box zinc-finger,and TRIM28 complexes in cancer to target tumor-suppressor proteins such as 5’ adenosine monopho-sphate-activated protein kinase(MAPK),which can promote the Warburg effect and hepatocellular carcinoma progression by targeting FBP1 for degradation.ZNF436 and TRIM28 may affect hepatocellular carcinoma progression together.Therefore,we decided to make use of clinical information and tests to study whether ZNF436 inhibit hepatocellular carcinoma progression by combining with TRIM28MethodsIn order to explore the level and relative prognosis of ZNF436 in the hepatocellular carcinoma,we collected and analyzed 60 cases of hepatocellular carcinoma in the Sir Run Run Shaw Hospital of Zhejiang University.Moreover,we explored its influence in proliferation,apoptosis and metastasis though construction of over expression of FLAG-ZNF436 lentivirus and overexpression of ZNF436 in two kinds of hepatocellular carcinoma cell lines,such as LM3.Spectrometry and bioinformatics database were used to explore protein interaction networks.What’s more,we also want to know the relationship between ZNF436 and TRIM28,whether ZNF436 though TRIM28 relative pathway to influence the occurrence and development of hepatocellular carcinoma.ResultsThere are same results that expression of ZNF436 was lower in hepatocellular carcinoma than normal tissue of liver,according to qPCR,Western Blot and immunohistochemistry.We found that cell proliferation ability decreased in LM3 cells with expression of ZNF436.There was significant difference in cell proliferation and apoptosis(P<0.05),while the abilities of metastasis have no statistical difference(P>0.05).According to Spectrometry and bioinformatics database,the relationship between ZNF436 and TRIM28 had been found.The level of ZNF436 and TRIM28 had the same trends to change in cells,especially in liver cells.ConclusionsWe found that ZNF436 is lower level in the hepatocellular carcinoma,while TRIM28 have the same result.The both of them maybe become the complex of ZNF436-TRIM28,and it contributed to promoting PBP1 and inhibition its degradation to inhibit hepatocellular carcinoma progression.