Abstract
Endometrial carcinoma (EC) is one of the most common malignancies of female reproductive tract in developed countries. MicroRNA is frequently dysregulated in human cancers and acts a key regulator role in tumor cell growth and metastasis. The aims of this study were to investigate the roles of microRNA-184 (miR-184) in EC cells and to identify its potential molecular mechanism. Here, the data revealed that miR-184 was significantly downregulated in human EC tissue compared with normal endometrial tissue, and the level of miR-184 expression was associated with lymph node metastasis and prognosis in patients with EC. In vitro assays, overexpression of miR-184 could suppress the proliferation and invasion of HEC-1B and RL95-2 cells. Moreover, bioinformatics analysis showed that cell division cycle 25A (CDC25A) was a putative target gene of miR-184. Dual luciferase reporter assay confirmed that miR-184 significantly downregulated CDC25A expression via directly interaction with the putative binding site in the 3'-untranslated region (3'-UTR) of CDC25A mRNA. Interestingly, knockdown of CDC25A resulted in inhibition of HEC-1B and RL95-2 cells growth and invasion. Mechanistic investigation revealed that downregulation of the Notch receptors (NOTCH1, NOTCH2, NOTCH3 and NOTCH4) and target gene HES1 by miR-184 could be reversed by CDC25A overexpression. In summary, our data demonstrate that CDC25A is a target gene of miR-184 in EC cells, and decreased expression of miR-184 suppresses the growth and invasion of EC cells via CDC25A-dependent Notch signaling pathway, suggesting that miR-184 may be a promising target for a new therapeutic strategy against EC.