Occurrence Of Epithelia-mesenchymal Transition In Endometrial Adenocarcinoma And The Roles Of MiR200a/ZEB1 Signaling Pathway In This Process

BackgroudEndometrial carcinoma is the most common type of female genital tract malignancy. Although endometrial carcinoma is a low grade curable malignancy, the condition of the disease can range from excellent prognosis with high curability to aggressive disease with poor outcome. The neoplasm invasiveness, the lymphatic metastasis and the distant metastasis have been known as the important factors to influence the EnCa’s outcome, relapse and mortality rate. People pay more and more attention to researching the source of EnCa’s invasive ability and how can malignant cells invade the normal tissue.Epithelia to mesenchymal transition (EMT) is a process which is described as the epithelia cells can downregulate epithelial characteristics and acquire mesenchymal characteristics. In the process, the epithelia cells lose the polarity, the adhesion between cells become loose and every cell acquire more motility. It is well-known that the metastasis to normal tissue is an important character of cancer cell. A lots of researches detected that EMT played an important role in breast cancer, colon cancer and epithelial ovarian cancer. The molecular mechanisms of EMT in EnCa is unclear, and the correlation research is rare during the word. We hope to finding out the way to investigating the molecular mechanisms involved in EMT in the EnCa.ObjectiveTo evaluate the different expression of e-cadherin, vimentin and ZEB1 between endometrium paraffin section and endometrial carcinoma paraffin section. To evaluate the expression of e-cadherin, vimentin, ZEB1 and miR200a in fresh endometrium and fresh endometrial carcinoma. We will also explore the regulatory relationships between these targets.MethodsThe expression of E-cadherin, Vimentin and ZEB1 were evaluated in endometrium paraffin section (n=22) and endometrial carcinoma paraffin section (n=45) by immunohistochemistry. The expression of E-cadherin, Vimentin and ZEB1 and their mRNA were evaluated in fresh endometrium (n=15) and fresh endometrial carcinoma (n=34) by Western blotting and Realtime RT-PCR. We also performed real-time PCR to quantify the expression of miR200a in both endometrium and endometrial carcinoma.Results① The expression of E-cadherin was decreased significantly in endometrial carcinoma compared with the endometrium. The expression of Vimentin and ZEB1 were increased significantly in endometrial carcinoma. ② Some significantly differences have been found in fresh sample. The E-cadherin and its mRNA was decreased in endometrial carcinoma. However, the Vimentin and its mRNA, the ZEB1 and its mRNA were all increased in endometrial carcinoma. ③ We found that the miR200a decreased significantly in endometrial carcinoma compared with endometrium. Through a linear regression analysis, we indicated that the miR200a was correlated significantly to the E-cadherin’s mRNA (R=0.63 P<0.01).Conclusions1. The biomarkers of EMT have a significative change between EnCa and endometrium. EMT occurs explicitly during endometrial carcinoma and it will not change with the progress of the disease.2. The expression of miR200a in EnCa is significantly lower than endometrium. Both the mRNAs and protein expression of ZEB1 (regulation target of miR200a) have increased significantly in EnCa. The mir200/ZEB signaling pathway may regulate the occurrence and progress of EMT in EnCa. However, we also find a linear correlation between miR200a and the mRNA of e-cadherin. MiR200a inhibits the occurrence of EMT in endometrial carcinoma by targeting the ZEB1.