The Function And Mechanism Of SUZ12 In Proliferation And Metastasis Of Hepatocellular Carcinoma

Background: Hepatocellular carcinoma is one of the most common malignancies in humans.The mortality rate rank the second in all malignancies,and the surgical treatment is the most conventional and most widely accepted treatment.However,the recurrence rate is high and the survival time is short.With the development of new medical means,such as radiofrequency ablation,interventional embolization and molecular targeted drug drug,the patients with liver cancer can live longer,but the effect of liver cancer treatment is still not ideal.The invasion and metastasis ability of liver cancer is the reason which cause shorter survival cycle,so the studying of the invasion and metastasis of liver cancer appear important.The occurrence of tumor is often accompanied by a gene mutation,leading to inhibition of the expression of tumor suppressor genes,oncogenes activation,gene mutation is inevitably accompanied by the change of gene structure,but in recent years,we found that the expressing of gene can change without the change of structure of gene,which we called gene epigenetic modifications.The gene epigenetic modifiction include DNA methylation and demethylation,histone acetylation and deacetylation,epigenetics provide a new direction for the research and treatment of cancer,.In gastric cancer,colon cancer and other tumor,we found that epigenetic changes can lead to chromosome gene instability and promote tumor formation.Therefore,it is particularly important to further study the role of epigenetic modification in the development and progression of HCC.SUZ12 is an important component of PRC2,which regulates tyrosinetrimethylation [1-3] at histone H3 27,and PRC2 inhibits the transcription of more than 1,000 genes in human embryonic fibroblasts [4].In the study of lung cancer,stomach cancer,colon cancer and breast cancer,we found that SUZ12 can promote the ability of invasion and metastasis [5-7] In the study of nausea glioma,we found that SUZ12 gene expression in the tumor is missing,the gene loss led to tumor cell transformation,achieving tumor cell characteristics [8].The expression of BAMBI,CCND2,DKK2,DLK1 and EpCAM were upregulated and the expression of SUZ12 and ZNF189 genes were down-regulated in HBV-related hepatocellular carcinoma(HCC).[9].The down-regulated of SUZ12 and ZNF198 expression can promote the replication of HBX and cause normal liver cells tranform to tumor cells.The decrease in the expression of SUZ12 and ZNF198,accompanied by upregulation of HOTAIR and PLK1 expression,cause changes in histone modifications.Therefore,SUZ12 plays an important role in the occurrence and development of HCC.However,the effect of SUZ12 on the proliferation,invasion and metastasis of HCC cells and its specific mechanisms are still unclear.OBJECTIVE: To study the expression of SUZ12 protein in hepatocellular carcinoma(HCC)and its role in the ability of invasion and metastasis of hepatocellular carcinoma(HCC).Methods: 1?The specimens of liver cancer were collected.The expression of SUZ12 in HCC was examined by Western blot,and the correlation was confirmed by statistics.2?To study the expression of SUZ12 in liver cancer tissues and adjacent tissues the relationship between SUZ12 and postoperative survival of cancer patients though the using of tissue microarray.3?Construct stable knockdown of SUZ12 hepatoma cell line,and SUZ12 over expression cell line though the using of lentivirus,the expression of suz12 wasexamed by western blot.The ability of invasion and migration of Hep3 b,SMMC-7721 tumor cell were examed by transwell assay.Western and blot were used to detect the changes of E-CADHERN,N-cadhern,Vimatin,,MMP-9,MMP-2 and PERK1/2 proteins in cell lines Hep3 b and SMMC-7721 after suz12 interference4?The change of proliferation ability of Hep3 b and SMMC-7721 afer suz12 overexpressed and interference were examed by MTT ? EDU and cells clone formation.5?The role of ERK signaling pathway in hepatocellular carcinoma cells invasion and migration ability were examed though using ERK signal transduction inhibitors.The changes of the ability of invasion and metastasis Hep3 b and SMMC-7721 after suz12 overexpressed and interference were examed by transwell and the protein of E-cadhern,N-cadhern,Vimatin,MMP-9,MMP-2,P-ERK1/2 were examed by western blot..Results:There are 20 cases liver cancer specimens which the suz12 protein in the tumor tissue is low than in the paracancerous tissue,tissue chip technology found that SUZ12 reduction can significantly reduce the survival of patients,in vitro experiments we found that the down-regulation of SUZ12 expression of liver cancer can increase the ability of invasion and migration.The expression of N-cadher protein in hep3 b and SMMC-7721 cells was significantly decreased and the expression of metal matrix enzyme mmp-9/2 and the protein of p-erk1 / 2 was significantly higher after the down-regulation of SUZ12,,The p-erk1 / 2 inhibitor was able to reverse the protein change of metal matrixase mmp-9 and mmp-2 in SUZ12-down-regulation cell lines.However,in the MTT experiment,EDU experiment we found that SUZ12 can not change the proliferation of Hep3 b and SMMC-7721.Conclusion:1?The survival cycle of HCC patients with low expression of SUZ12 and decreased SUZ12 in HCC was significantly shorter than that in patients without SUZ12 and elevated SUZ12.2?The deletion and over expression of SUZ12 had no significant influence on the proliferation ability of HCC cell line Hep3 b and SMMC-77213?The deletion of SUZ12 promotes phosphorylation of P-ERK1/2,activates the ERK signaling pathway and promotes the migration and invasion of HCC cell lines Hep3 b and SMMC-7721...