Yonsei Med J.  2021 Jun;62(6):535-544. 10.3349/ymj.2021.62.6.535.

DNM3OS Facilitates Ovarian Cancer Progression by Regulating miR-193a-3p/MAP3K3 Axis

• He L
• He G

• KMID: 2516086
• DOI: http://doi.org/10.3349/ymj.2021.62.6.535

Abstract

Purpose
Long non-coding RNAs (lncRNAs) are essential regulators in the development of ovarian cancer (OC). Nonetheless, the function of lncRNA DNM3 opposite strand/antisense RNA (DNM3OS) in OC remains unclear. This work aimed to investigate the biological roles and underlying mechanisms of DNM3OS in OC.
Materials and Methods
Quantitative real-time polymerase chain reaction was conducted to examine DNM3OS, microRNA (miR)-193a-3p, and mitogen-activated protein kinase 3 (MAP3K3) mRNA expression in OC tissues and cell lines. Kaplan-Meier survival analysis was employed to analyze the relationship between DNM3OS expression and the prognosis of OC patients. Cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and transwell experiments were conducted to monitor cell proliferation, migration, and invasion, respectively. Western blot was applied to examine epithelial-mesenchymal transition associated protein (E-cadherin and N-cadherin) expression. Luciferase reporter gene and RNA immunoprecipitation experiments were performed to confirm the relationships among DNM3OS, miR-193a-3p, and MAP3K3. Pearson’s correlation analysis was adopted to analyze the correlations among DNM3OS, miR-193a-3p, and MAP3K3 mRNA.
Results
DNM3OS expression was remarkably increased in OC tissues and cell lines, which was associated with the unfavorable prognosis of the patients. DNM3OS overexpression enhanced OC cell proliferation, migration, and invasion; suppressed E-cadherin protein expression; and facilitated N-cadherin protein expression, while the transfection of miR-193a-3p mimics had the opposite effects. DNM3OS directly interacted with miR-193a-3p, and miR-193a-3p targeted MAP3K3 by directly binding to 3'UTR. DNM3OS could up-regulate the expression of MAP3K3 via repressing miR-193a-3p expression.
Conclusion
DNM3OS, as an oncogenic lncRNA, increases the malignancy of OC cells via regulation of an miR-193a-3p/MAP3K3 axis.

Keyword

lncRNA; DNM3OS; miR-193a-3p; MAP3K3; ovarian cancer