The Effect Of S100A8 In Endometrial Cancer And Its Regulating Mechanisms

Objective:Endometrial cancer is one of the three major malignant tumors in the female reproductive system.The data show that the incidence of endometrial cancer s is increasing year by year.S100A8 can directly or indirectly affect the proliferation,invasion and migration of various tumors by activating related signal molecules.This study explored whether S100A8 is related to the clinical characteristics of the patients,whether it can be used as a molecular marker for early diagnosis and prognosis of endometrial cancer,S100A8 is a possible molecular mechanism regulating development of endometrial carcinoma.To provide a meaningful guidance for early prevention,early diagnosis,clinical treatment and prognosis of endometrial carcinoma.Methods:1.In clinical trials,22 specimens of normal endometrium and 74 endometrioid adenocarcinoma specimens were collected to explore the role of S100A8 in the occurrence and development of endometrial carcinoma by detecting the protein expression level and RNA expression level of S100A8 in normal endometrium and endometrial carcinoma tissues.2.The basic experimental part consists of 2 parts,the interference group and the overexpression group.As indicated by the interference group,the S100A8 gene of the HEC-1A cell line was knocked out by the micro RNA interference technique,the experimental group(sh-S100A8),the blank control group(NC-SH-S100A8)and the wild control group(HEC-1A)were constructed,and the cell lines were successfully constructed by Western Blot and qRT-PCR experiments,and then MTT,flow cytometry,and cells were followed.We tested the effect of S100A8 on the biological behavior of endometrial carcinoma cell lines and the related mechanisms were explored.Results:1.The expression of S100A8 protein and S100A8 mRNA are highly expressed in in endometrial.The S100A8 protein is expressed in the cell membrane and cytoplasm of the tumor cells in the high and middle differentiation groups of endometrial carcinoma.But in the low differentiation group,the S100A8 protein is diffused in any part of the tumor cells.The positive expression rate of S100A8 protein in poorly differentiated group was 95.45%,which was different from the positive expression rate 73.47% in high and middle differentiation groups,(P<0.05).2.Compared with the control group,the expression of S100A8 protein and S100A8 mRNA in the experimental group was obviously reduced.The results of cell experiment showed that the proliferation of the cells in the experimental group was reduced,the apoptosis in the early stage of the cell was increased.After knock off the S100A8,the phosphorylation process of AKT was blocked and the expression of apoptosis related genes,such as Cytochrome C,Bad,Bax,FOXO1 and Caspase-3 were increased.3.The expression of S100A8 gene and protein in HEC-1-A cells can be effectively increased by lentivirus transfection.The expression of S100A8 gene can affect the biological behavior of HEC-1-A cell proliferation and migration.The cell proliferation and migration ability of the experimental group(S100A8-OE)increased as compared with that of the wild control group.Conclusions:1.Compared with the normal endometrium,the expression of S100A8 was highly expressed in endometrium carcinoma,and the expression level was positively correlated with the tumor histological staging of the patients.Therefore,it was concluded that S100A8 could be used as a biomarker for the early diagnosis of endometrial cancer.2.Interfered S100A8 can promote the apoptosis of endometrial carcinoma cells and inhibit its proliferation.Therefore,it is concluded that S100A8 can be used as a biological target for targeting treatment of endometrial cancer.3.Overexpression of cadherin S100A8 can promote the proliferation and migration of endometrial cancer cells.Therefore,it is concluded that S100A8 can be used as a biomarker for follow-up and prognosis of endometrial cancer.