MiR-338-3p Enhances Ovarian Cancer Cell Sensitivity to Cisplatin by Downregulating WNT2B

PURPOSE: Chemoresistance is a concern in ovarian cancer patients, in whom survival remains. MicroRNA, a novel class of small RNAs, 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 mechanisms thereof. MATERIALS AND METHODS: The expression levels of miR-338-3p and WNT2B in ovarian cancer tissues and cells were estimated by real-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 blot assay was conducted to measure protein expression of WNT2B, epithelial-mesenchymal transition (EMT)-related proteins, and apoptosis-related proteins. The relationship between miR-338-3p and WNT2B was confirmed by dual-luciferase reporter. Finally, a xenograft tumor model was developed to explore the effects of overexpression of miR-338-3p on tumor growth in ovarian cancer in vivo. RESULTS: MiR-338-3p was downregulated in cisplatin resistant ovarian cancer tissues and cells. Mechanistically, high expression of miR-338-3p enhanced cell sensitivity to cisplatin by inhibiting proliferation, motility, and EMT and by promoting apoptosis via targeting WNT2B expression in vitro. Furthermore, overexpression of miR-338-3p increased cisplatin sensitivity among ovarian cancer in an in vivo xenograft tumor model. CONCLUSION: MiR-338-3p enhances the sensitivity of ovarian cancer cells to cisplatin by downregulating WNT2B.

miR‑338‑3p suppresses epithelial‑mesenchymal transition and metastasis in human nonsmall cell lung cancer.

OBJECTIVES: MicroRNAs are important modulators of the cellular epithelial‑mesenchymal transition (EMT) process and are associated with metastasis in human nonsmall cell lung cancer (NSCLC). In this study, we tried to investigate the role of miR‑338‑3p in NSCLC cells. MATERIALS AND METHODS: Real‑time polymerase chain reaction was applied to quantify the expression levels of miR‑338‑3p, as well as EMT‑associated molecules in NSCLC cells. Wound healing and transwell assays were performed to evaluate the migration and invasion capacities, respectively. Dual‑luciferase reporter assay was finally performed to determine the targeting of zinc finger E‑box‑binding protein 2 (ZEB2) by miR‑338‑3p. RESULTS: We found that miR‑338‑3p was significantly reduced in NSCLC cell lines. Forced expression of miR‑338‑3p in A549 cells led to the suppression of migration/invasion capacity and inhibition of epithelial markers. In addition, we proved that miR‑338‑3p could directly target ZEB2. CONCLUSIONS: In general, we summarized that miR‑338‑3p could inhibit EMT and metastasis of human NSCLC cells, which probably via directly targeting ZEB2 expression.