MicroRNA-423 promotes proliferation, migration and invasion and induces chemoresistance of endometrial cancer cells.

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.