MicroRNA-135a promotes proliferation, migration, invasion and induces chemoresistance of endometrial cancer cells

AIMS: MicroRNAs play essential roles in tumorigenesis and progression in various cancers including endometrial cancer. Here we assessed the role of miR-135a on proliferation, chemosensitivity, migration and invasion of endometrial cancer cells. METHODS: WST-1 assay was performed to examine the proliferation of HEC-1-B and ISHIKAWA endometrial cancer cells with altered expression of miR-135a, with or without cisplatin treatment. Transwell migration and matrigel invasion assays were used to assess the migration and invasion of endometrial cancer cells. The Caspase-Glo3/7 assay was used to examine the effect of miR-135a on cisplatin-induced apoptosis of endometrial cancer cells. The dual-luciferase reporter assay was conducted to validate the putative binding site. RESULTS: Upregulation of miR-135a improved the proliferation, and promoted migration and invasion of endometrial cancer cells. Furthermore, miR-135a decreased the sensitivity of HEC-1-B and ISHIKAWA cells after cisplatin treatment. The cisplatin-induced apoptosis in endometrial cancer cells was inhibited by miR-135a by regulation of BAX and Bcl-2 expression. Meanwhile, miR-135a could regulate epithelial to mesenchymal transition (EMT) by altering the expression of E-cadherin, N-cadherin, snail and Vimentin in endometrial cancer cells. Further study showed that the expression levels of PTEN and p-AKT in endometrial cancer cells were changed after aberrant expression of miR-135a. CONCLUSION: MiR-135a played important roles in tumorigenesis and disease progression of endometrial cancer by regulating proliferation and chemosensitivy of endometrial cancer cells by targeting AKT signaling pathway. Our study indicates that miR-135a might act as a potential biomarker to predict chemotherapy response and prognosis in endometrial cancer.