BCL11A Is Expressed And Has Important Functions In Endometrial Adenocarcinoma

Objective : We are interested in BCL11A's expression and function in endometrial adenocarcinoma. We analysed the expression of BCL11 in endometrial adenocarcinoma and revealed the relationship between the expression of BCL11 A, MDM2 and clinicopathological features. We further explored BCL11 A in the occurrence of EAC and the possible molecular mechanisms. Our study aims to provide theoretical foundation of the occurrence of EAC and to dissect genes that have a driving role in the occurrence of EAC, which can lead to new revenues for the early diagnosis and eventually targeted therapy of EAC.Methods : 1) The expression of BCL11 A in EAC and NE tissues and the relationship between the expression of BCL11 A, MDM2 and clinicopathological features were analysed by combining TMA and IHC. 2) We used BCL11 A sh RNA to knock down its expression in CCK-8 and HEC-1-B cells. The functional consequences of BCL11 A knockdown were examined in in vitro assays including proliferation, colony formation, cell detachment, cell migration and invasion of cells, and.in vivo tumour cell engraftment in nude mouse. 3) We performed FCM to observe the effect of BCL11 A on the cell cycle in HEC-1-B cells. Furthermore, we detected the expression changes of MDM2?P21 in HEC-1-B cells by WB, and in tumours by IHC, after BCL11 A knockdown. 4) Finally, using SPSS 19.0 software, we performed statistical analyses of the results in this study. P value of less than 0.05 was considered statistically significant.Results: 1) We measured the expression levels and subcellular localization of BCL11 A in 108 EAC and 23 NE samples using IHC. Specific BCL11 A protein staining was found in the cytoplasm of non-cancerous and malignant epithelial cells. Furthermore, the expression levels of BCL11A were significantly higher in the EAC samples than that in the NE samples(?2=4.368,P<0.05. And the expression levels were negatively correlated with tumor pathological stage and tumor size, but not age or lymph node status related. These results indicate that BCL11 A may play a role in these tumours. We also analysed the correlation between the expression of BCL11 A and MDM2. The expression levels of BCL11 A were significantly positively correlated with that of MDM2 in the EAC samples(R2=0.3971, P<0.0001). 2) BCL11 A knockdown in CCK-8 cells significantly reduced proliferation and clonony formation(P<0.05). In cell detachment test and Transwell experiments, the migration and invasion abilities of HEC-1-B-BCL11a-sh RNA group also significantly decreased(P<0.05). Importantly, the engrafted HEC-1-B-BCL11a-sh RNA cells had lower tumour formation potential(P<0.05). 3) Mechanistically, BCL11 A knockdown caused G1 arreat in HEC-1-B- BCL11a-sh RNA cells in FCM. Western blot confirmed that BCL11 A knockdown resulted in down-regulation of MDM2 but increased P21.lower MDM2 and higher P21.Conclusion: 1) Expression in primary tumours and in tumours formed from BCL11 A kncodown cells indicate that BCL11 A may have important functions in EAC. 2) BCL11 A regulates cell proliferation, migration and tumorigenic formation in vitro and in vivo assays. Molecularly, BCL11 A is to control cell cycle especially the G1/S checkpoint through regulating MDM2.