MiR-338-3p Enhances Ovarian Cancer Cell Sensitivity to Cisplatin by Downregulating WNT2B
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Purpose: Chemoresistance is a concern in ovarian cancer patients, in whom survival remains. MicroRNA, a novel class of smallRNAs, have frequently been found to be dysregulated in human malignancies and to act as negative regulators of gene expression. This study aimed to explore the function of miR-338-3p in cisplatin resistance in ovarian cancer and potential molecular mechanismsthereof. Materials and Methods: The expression levels of miR-338-3p and WNT2B in ovarian cancer tissues and cells were estimated byreal-time quantitative polymerase chain reaction (RT-qPCR). In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and flow cytometry assays were used to assess biological role of miR-338-3p in vitro. Western blotassay was conducted to measure protein expression of WNT2B, epithelial-mesenchymal transition (EMT)-related proteins, andapoptosis-related proteins. The relationship between miR-338-3p and WNT2B was confirmed by dual-luciferase reporter. Finally, axenograft tumor model was developed to explore the effects of overexpression of miR-338-3p on tumor growth in ovarian cancerin vivo. Results: MiR-338-3p was downregulated in cisplatin resistant ovarian cancer tissues and cells. Mechanistically, high expression ofmiR-338-3p enhanced cell sensitivity to cisplatin by inhibiting proliferation, motility, and EMT and by promoting apoptosis via targetingWNT2B expression in vitro. Furthermore, overexpression of miR-338-3p increased cisplatin sensitivity among ovarian cancerin an in vivo xenograft tumor model. Conclusion: MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B.
Abstract
Purpose: Chemoresistance is a concern in ovarian cancer patients, in whom survival remains. MicroRNA, a novel class of smallRNAs, have frequently been found to be dysregulated in human malignancies and to act as negative regulators of gene expression. This study aimed to explore the function of miR-338-3p in cisplatin resistance in ovarian cancer and potential molecular mechanismsthereof. Materials and Methods: The expression levels of miR-338-3p and WNT2B in ovarian cancer tissues and cells were estimated byreal-time quantitative polymerase chain reaction (RT-qPCR). In addition, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT), transwell, and flow cytometry assays were used to assess biological role of miR-338-3p in vitro. Western blotassay was conducted to measure protein expression of WNT2B, epithelial-mesenchymal transition (EMT)-related proteins, andapoptosis-related proteins. The relationship between miR-338-3p and WNT2B was confirmed by dual-luciferase reporter. Finally, axenograft tumor model was developed to explore the effects of overexpression of miR-338-3p on tumor growth in ovarian cancerin vivo. Results: MiR-338-3p was downregulated in cisplatin resistant ovarian cancer tissues and cells. Mechanistically, high expression ofmiR-338-3p enhanced cell sensitivity to cisplatin by inhibiting proliferation, motility, and EMT and by promoting apoptosis via targetingWNT2B expression in vitro. Furthermore, overexpression of miR-338-3p increased cisplatin sensitivity among ovarian cancerin an in vivo xenograft tumor model. Conclusion: MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B.
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