Yonsei Med J.  2019 Dec;60(12):1146-1156. 10.3349/ymj.2019.60.12.1146.

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

Affiliations
  • 1Department of Oncology, The First People's Hospital of Lianyungang, Lianyungang, China. lyg82072010@163.com

Abstract

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.

Keyword

WNT2B; miR-338-3p; ovarian cancer; chemoresistance

MeSH Terms

Apoptosis
Blotting, Western
Cisplatin*
Epithelial-Mesenchymal Transition
Flow Cytometry
Gene Expression
Heterografts
Humans
In Vitro Techniques
MicroRNAs
Ovarian Neoplasms*
Polymerase Chain Reaction
RNA
Cisplatin
MicroRNAs
RNA
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