The Effect Of MTA1on The Invasion And Migration Of Endometrial Carcinoma

ObjectMTA1(metastasis-associated gene1) is a newly discovered cancer progression-related gene. MTA1proteins are transcriptional co-repressors that function in histone deacetylation and are involved in the NuRD complex (nucleosome remodeling and histone deaeetylase). MTA1protein may serve multiple functions in cellular signaling, chromosome remodeling and transcription processes that are important in the progression, invasion and growth of cancer. MTA1has been repeatedly reported to be overexpressed in a wide range of human cancers,such as Lung cancer, liver cancer, pancreatic cancer,and esophageal cancer etal and related with the invasion and migration of these tumors. However the study in the role of MTA1in endometrial carcinoma is rare.This study investigated the difference among different endometrial tissue and the effect of MTA1on invasion and migration of endometrial carcinoma cell line HEC-1-A by depressing the expression of MTA1by specific siRNA(short interfering RNA)targeting MTA1and explored the role of MTA1in the invasion and migration of endometrial carcinoma,and provide potential target gene in the therapy of endometrial carcinoma along with the theoretical basis.Methods1. MTA1protein expression of499cases of endometrial tissue was detected by immunohistochemistry. In this study,100cases of normal endometrial tissue,49cases of dysplasia endometrial tissue and300cases of endometrial carcinoma tissue were involved. We analyzed the difference of the MTA1protein expression among the groups mentioned above and explored the relationship between the clinical features of endometrial carcinoma such as pathologic grades, clinical stages and depth of myometrial invasion.2. The specific siRNA expression vector psilencer2.0-MTA1-siRNA was transfected into HEC-1-A cells by liposome. The groups of unrelated-sequence expression vector psilencer2.0-neg and non-transfected were as control. 3. The expression of mRNA and protein of MTA1were detected by RT-PCR and western blot assay, respectively.4. Invasion and migration ability was evaluated by scrape wound healing assay, and transwell assay. This study verified the feasibility of inhibiting the invasion and migration of endometrial carcinoma by RNA interference targeting MTA1in vitro.Results1. The expression of MTA1protein was significantly different in normal endometrial tissue, dysplasia endometrial tissue and (p<0.001) and the level of expression was significantly high in the endometrial carcinoma tissue The expression of MTA1was negatively associated with pathologic grades and positively associated with clinical stages and the depth of myometrial invasion.2. RT-PCR and western blot showed that the expression of mRNA and protein of MTA1were depressed effectively. The scrap wound healed more slowly and the relative percentage of HEC-1-A cells which cut through Matrigel decreased in the group transfected by siRNA.Conclusions1. MTA1was closely related to pathogenesis, pathologic grades, clinical stages and myometrial invasion endometrial carcinoma. MTA1may play an important role in the pathogenesis and development of endometrial carcinoma, and may become a biological predictor for the pathogenesis, development and the recurrence of endometrial carcinoma. This study provided basis for the diagnosis and treatment of endometrial carcinoma.2. The experiments in vitro showed that siRNA targeting MTA1depressed the expression of MTA1mRNA and protein and then the ability of invasion and migration in HEC-1-A cells was inhibited. It indicated that MTA1played an important role in the invasion and migration of endometrial carcinoma and may become a new potential target in the therapy of endometrial carcinoma.