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MicroRNA-365 inhibits ovarian cancer progression by targeting Wnt5a
Yanli Wang1, Chunling Xu2, Yun Wang3
1Department of Gynecology, The First Hospital of Jilin UniversityChangchun 130021, China.
Abstract:
MicroRNA-365 (miR-365) has been reported to play an important role in tumorigenesis in many types of cancers; however, the role of miR-365 in the carcinogenesis of ovarian cancer remains unknown. In this study, we focused on the roles and underlying mechanisms of miR-365 in ovarian cancer. Here, we found that miR-365 expression level was significantly decreased in ovarian cancer tissues and cell lines, and that low miR-365 expression was negatively significantly associated with advanced stages as defined by the International Federation of Gynecology and Obstetrics (FIGO), histological grading, and lymph node metastasis. Further functional assays showed that transfection with a miR-365 mimic significantly decreased ovarian cancer cell proliferation, colony formation, migration, and invasion. In addition, Wnt5a was identified as a target gene of miR-365 in ovarian cancer by bioinformatic analysis, luciferase reporter assay, qPCR, and western blot. Wnt5a expression levels were upregulated and inversely correlated with miR-365 expression in ovarian cancer tissues (r = -0.638, P < 0.0001). Overexpression of Wnt5a could effectively reverse the miR-365 overexpression-induced suppression of proliferation and invasion in ovarian cancer cells. Additionally, in vivo studies utilizing a xenograft model demonstrated that overexpression of miR-365 could reduce tumor growth by repressing Wnt5a. Taken together, these findings suggest that miR-365 may be a promising candidate for therapeutic application in ovarian cancer treatment.
Insights
MicroRNA-365 (miR-365) is decreased in ovarian cancer, suppressing tumor growth and invasion by targeting Wnt5a. This suggests miR-365 is a potential therapeutic target for ovarian cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The role of microRNA-365 (miR-365) in ovarian cancer development is largely unknown.
- Previous studies indicate miR-365's involvement in tumorigenesis across various cancers.
- Ovarian cancer remains a significant global health challenge requiring novel therapeutic strategies.
Purpose of the Study:
- To investigate the function and molecular mechanisms of miR-365 in ovarian cancer.
- To determine the relationship between miR-365 expression and clinicopathological features of ovarian cancer.
- To identify potential therapeutic applications of miR-365 in ovarian cancer.
Main Methods:
- Quantitative real-time PCR (qPCR) and Western blot analysis to assess miR-365 and Wnt5a expression.
- Functional assays including cell proliferation, colony formation, migration, and invasion assays.
- Bioinformatic analysis, luciferase reporter assays, and xenograft mouse models to validate miR-365 targets and mechanisms.
Main Results:
- miR-365 expression was significantly downregulated in ovarian cancer tissues and cell lines.
- Low miR-365 expression correlated with advanced FIGO stage, poor histological grade, and lymph node metastasis.
- miR-365 mimic transfection inhibited ovarian cancer cell proliferation, migration, and invasion.
- Wnt5a was identified as a direct target of miR-365, with inverse correlation in patient tissues.
- Wnt5a overexpression reversed the anti-proliferative and anti-invasive effects of miR-365.
- In vivo studies confirmed that miR-365 overexpression suppressed tumor growth by repressing Wnt5a.
Conclusions:
- miR-365 functions as a tumor suppressor in ovarian cancer by inhibiting proliferation, migration, and invasion.
- The miR-365/Wnt5a axis plays a critical role in ovarian cancer progression.
- miR-365 represents a potential biomarker and therapeutic target for ovarian cancer.
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