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

다국어 초록 (Multilingual Abstract)

Purpose: Long non-coding RNAs (lncRNAs) are essential regulators in the development of ovarian cancer (OC). Nonetheless, thefunction of lncRNA DNM3 opposite strand/antisense RNA (DNM3OS) in OC remains unclear. This work aimed to investigate thebiological 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-Meiersurvival analysis was employed to analyze the relationship between DNM3OS expression and the prognosis of OC patients. Cellcounting 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-cadherinand N-cadherin) expression. Luciferase reporter gene and RNA immunoprecipitation experiments were performed to confirmthe relationships among DNM3OS, miR-193a-3p, and MAP3K3. Pearson’s correlation analysis was adopted to analyze thecorrelations 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 unfavorableprognosis of the patients. DNM3OS overexpression enhanced OC cell proliferation, migration, and invasion; suppressed E-cadherinprotein expression; and facilitated N-cadherin protein expression, while the transfection of miR-193a-3p mimics had the oppositeeffects. 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.

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