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Published on: August 2, 2024
DNM3OS Facilitates Ovarian Cancer Progression by Regulating miR-193a-3p/MAP3K3 Axis
1Department of Gynecology and Obstetrics, Key Laboratory of Obstetrics and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, China.
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.
Insights
Long non-coding RNA DNM3OS promotes ovarian cancer (OC) progression by enhancing cell proliferation, migration, and invasion. This oncogenic lncRNA functions through an miR-193a-3p/MAP3K3 signaling axis, indicating a potential therapeutic target for OC.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) play crucial roles in cancer development.
- The specific function of lncRNA DNM3 opposite strand/antisense RNA (DNM3OS) in ovarian cancer (OC) is not well understood.
Purpose of the Study:
- To investigate the biological roles of DNM3OS in OC.
- To elucidate the underlying molecular mechanisms of DNM3OS in OC progression.
Main Methods:
- Quantitative real-time PCR and Western blot to assess gene and protein expression.
- Cell proliferation, migration, and invasion assays (CCK-8, EdU, Transwell).
- Luciferase reporter and RNA immunoprecipitation assays to confirm molecular interactions.
Main Results:
- DNM3OS expression is upregulated in OC tissues and associated with poor prognosis.
- DNM3OS overexpression promotes OC cell proliferation, migration, and invasion, and epithelial-mesenchymal transition (EMT).
- DNM3OS directly interacts with miR-193a-3p, which targets MAP3K3, forming an miR-193a-3p/MAP3K3 axis.
Conclusions:
- DNM3OS acts as an oncogenic lncRNA in ovarian cancer.
- DNM3OS promotes OC malignancy by regulating the miR-193a-3p/MAP3K3 axis.
- DNM3OS represents a potential therapeutic target for ovarian cancer treatment.
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