Abstract
Altered microRNA expression serves essential roles in tumorigenesis and progression in endometrial cancer. In the present study the effect of miR-423 on proliferation, chemosensitivity, migration and invasion of endometrial cancer cells was examined. A WST-1 assay was used to examine the proliferation of HEC-1B and Ishikawa endometrial cancer cells with either upregulation or downregulation of miR-423, with or without cisplatin treatment. The migration and invasion of HEC-1B and Ishikawa endometrial cancer cells were examined via Transwell migration and Matrigel invasion assays. Protein expression levels, including B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein, E- and N-cadherin, snail, vimentin, phosphatase and tensin homolog (PTEN) and protein kinase B (AKT) were examined by western blotting. A caspase-Glo3/7 assay was carried out to evaluate the effect of miR-423 on cisplatin-induced apoptosis in HEC-1B and Ishikawa endometrial cancer cells. Overexpression of miR-423 enhanced the proliferation, and increased migration and invasion in endometrial cancer cells. miR-423 also decreased the sensitivity of endometrial cancer cells following cisplatin treatment. miR-423 inhibited cisplatin-induced apoptosis in endometrial cancer cells by regulation of caspase 3/7 and Bcl-2 expression. Furthermore, the E-cadherin expression was significantly decreased, and the expression of N-cadherin, snail and Vimentin were increased in both HEC-1B cells and Ishikawa cells following overexpression of miR-423. Conversely, downregulation of miR-423 increased the expression of E-cadherin and decreased the expression of N-cadherin, snail and Vimentin. Further experiments demonstrated that the expression levels of PTEN and phosphorylated-AKT in HEC-1B and Ishikawa endometrial cancer cells was decreased and increased, respectively, following aberrant expression of miR-423. miR-423 displayed an important role in tumorigenesis and progression in endometrial cancer cells, and may therefore be used as a potential biomarker to predict chemotherapy response and prognosis in endometrial cancer.