CircHIPK3 Affects The Activities Of Esophageal Squamous Cancer Cells By Regulating P53-Akt-Mdm2 Signaling Pathways

Objective: Esophageal cancer is a kind of disease with high morbidity and mortality,the five year survival rate of advanced esophageal cancer is lower than that of 15%,but that of patients with early esophageal cancer is more than 80%.But early esophageal cancer is difficult to diagnose.The purpose of this study was to find out the relationship between CircHIPK3 and esophageal cancer by studying CircHIPK3 in esophageal cancer,and to find out a new way of thinking in the diagnosis and targeted therapy of esophageal cancer.Methods : In this study,the clinical specimens of 11 patients with cancer and paracancerous tissue were collected.The tumor tissue was used as the experimental observation group and the adjacent cancer tissue as the blank control group.The real-time quantitative pcr detection was performed on all the tissue samples of the observation group and the control group.Lentiviral vector was transfected into EC9706 cell line.Four groups of cells were constructed: high expression group of CircHIPK3,high expression control group,low expression group and low expression control group.Then the effects of CircHIPK3 on cell proliferation,invasion,migration and apoptosis were detected by cck-8,transwell and flow cytometry,respectively.Finally,bioinformatics analysis was used to determine the possible pathway of CircHIPK3,and western blot was used to verify its pathway-related functional proteins.Results: Real-time quantitative PCR,showed abnormal expression of CircHIPK3 in 11 cancer tissues and 7 paracancerous tissues(P=0.027).The high expression of CircHIPK3 increased the proliferation(P<0.001),migration(P<0.001)and invasion(P<0.001)ability of the cells,but decreased at the low expression level.The apoptosis of EC9706 cells overexpressed with CircHIPK3 was inhibited,and the apoptosis was promoted by low expression.The tumor suppressor gene p53 was significantly inhibited in cells with high expression of CircHIPK3,and the intracellular akt-mdm2 signaling pathway is activated,The expression of p53-akt-mdm2 pathway protein increased accordingly.Ultimately,cancer cell proliferation,migration,invasion,and cancer protein expression are enhanced.The function of cancer cells was enhanced.On the contrary,low expression of CircHIPK3 can inhibit the function of cancer cells.Conclusions: CircHIPK3 promotes proliferation,migration and invasion of human esophageal cancer cells,and inhibits apoptosis,this may be achieved by regulating the p53-akt-mdm2 signaling pathway.Therefore,based on our findings,CircHIPK3 may be a potential target for esophageal cancer.