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MiR-498 regulated FOXO3 expression and inhibited the proliferation of human ovarian cancer cells
Ruonan Liu1, Fenghua Liu1, Lei Li1
1Department of Gynecology, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, People's Republic of China.
Abstract:
Ovarian cancer is one of the most common human malignancies and the fifth leading cause of cancer deaths in women. Thus, improved approaches for detection of ovarian cancer are urgently needed. Recently, microRNAs (miRNAs) have been suggested to be closely associated with ovarian cancer tumorigenesis. In the current study, our study showed that expression of miR-498 was markedly downregulated in ovarian cancer cells and ovarian cancer tissues compared with human ovary surface epithelial cells (HOSE) and the matched tumor adjacent normal tissues (ANT). Ectopic expression of miR-498 suppressed cell proliferation of ovarian cancer cells, while i miR-498-in showed the opposite effect. Furthermore, upregulation of miR-498 in ovarian cancer cells resulted in blocking of their entry into the S transitional phase, which was caused by downregulation of the CDK regulator cyclin D1 and upregulation of cyclin-dependent kinase inhibitor p27. Additionally, we identified FOXO3 as a direct target of miR-498. Moreover, we demonstrated that miR-498 upregulated FOXO3 expression by directly targeting the FOXO3 3'-untranslated region. Thus, our findings suggested that miR-498 acted as a new tumor suppressor by targeting the FOXO3 gene and inhibiting cell proliferation of ovarian cancer.
Insights
MicroRNA-498 (miR-498) is downregulated in ovarian cancer. Restoring miR-498 suppresses ovarian cancer cell proliferation by targeting the FOXO3 gene, indicating its role as a tumor suppressor.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Ovarian cancer is a leading cause of cancer death in women, necessitating improved detection and treatment strategies.
- MicroRNAs (miRNAs) are increasingly recognized for their roles in cancer development, including ovarian cancer tumorigenesis.
Purpose of the Study:
- To investigate the role of miR-498 in ovarian cancer.
- To identify the molecular mechanisms by which miR-498 affects ovarian cancer cell behavior.
Main Methods:
- Quantitative real-time PCR to measure miR-498 expression in ovarian cancer tissues and cells.
- Cell proliferation assays to assess the functional impact of miR-498.
- Western blotting to analyze protein expression levels of cell cycle regulators (cyclin D1, p27) and FOXO3.
- Luciferase reporter assays to confirm direct targeting of FOXO3 by miR-498.
Main Results:
- miR-498 expression was significantly downregulated in ovarian cancer tissues and cells compared to normal controls.
- Ectopic expression of miR-498 inhibited ovarian cancer cell proliferation and blocked cell cycle progression at the S phase.
- miR-498 downregulation of cyclin D1 and upregulation of p27 contributed to the observed cell cycle arrest.
- FOXO3 was identified as a direct target of miR-498, with miR-498 regulating FOXO3 expression via its 3'-untranslated region.
Conclusions:
- miR-498 functions as a tumor suppressor in ovarian cancer.
- The miR-498/FOXO3 axis plays a critical role in regulating ovarian cancer cell proliferation.
- miR-498 represents a potential therapeutic target for ovarian cancer treatment.
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