Expression And Clinical Significance Of H3K27 Methylation Regulating Enzyme JMJD3, UTX And EZH2 In Endometrial

Objective: To detect expression of H3K27demethylase JMJD3, UTX and methyltransferase EZH2in endometrial adenocarcinoma and normal endometrium, and analyze their clinical significance.Methods:We analyzed the three gene’s expression database through Oncomine website. Expression level of JMJD3, UTX and EZH2in cell lines (Hec-1A, Ishikawa, Hec-1B, K1E, RL95-2and two primary endometrial epithelial cells) were detected by real-time PCR and western blot. Immunocytochemistry wase used to confirm the protein expression of JMJD3. mRNA expression was measured by real-time PCR analysis in27type I endoemetrial endometrioid adenocarcinoma tissues and17normal endometrium tissues. The EZH2protein expression levels were measured by immunohistochemical analysis in49type I endometrial endometrioid adenocarcinoma tissues and35normal endometrium tissues. Kruskal-Wallis H(K) test was used to assess the correlation between the expression profiles and clinicopathological parameters.Results:Oncomine results showed a higher mRNA expression level of JMJD3and UTX in Type Iendometrial adenocarcinomas compared to normal endometrium. But for EZH2, the H3K27methyltransferase, no obvious difference between these two groups was observed. We confirmed that the mRNA and protein expression of JMJD3and UTX were higher in cancer cells compared to normal endometrial epithelial cells (EECs) significantly (P<0.05). The mRNA expression levels of JMJD3, UTX and EZH2were all increased in cancer tissues compared to normal tissues, though it was statistically insignificant (P value=0.632,0.138and0.595, respectively). Unlike the results from Oncomine database, the mRNA and protein level of EZH2were increased in the endometrial cancer cell lines compared to normal EECs. Furthermore,the protein expression level of EZH2was increased in cancer tissues (P=0.005), and high EZH2expression was significantly associated with LVSI. Patients with EZH2overexpression were present with more aggressive behavior.Conclusions: Our study demonstrated that H3K27methyltransferase EZH2was upregulated in endometrial adenocarcinomas and associated with LVSI, indicating EZH2may play roles in the development of endometrial adenocarcinomas. Both H3K27demethylase (UTX and JMJD3) and methyltransferase (EZH2) were upregulated in endometrial adenocarcinomas validate the need for further study of their potential roles in oncogenesis.