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MiR-214 suppressed ovarian cancer and negatively regulated semaphorin 4D
Yang Liu1, Honglin Zhou1, Lan Ma2
1Department of Gynecology, The Second Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, People's Republic of China.
Abstract:
Ovarian cancer is one of the most common human malignancies in women. MiR-214 and semaphorin 4D (sema 4D) were found to be abhorrently expressed and involved in the progress of several kinds of malignant cancers. This study is aimed to investigate the cellular role of miR-214 and demonstrate that miR-214 negatively regulated sema 4D in ovarian cancer cells. The data showed that miR-214 expression was consistently lower in ovarian cancer tissues and cells than those in the normal controls. Over-expression of miR-214 in ovarian cancer SKOV-3 cells inhibited cell proliferation and induced apoptosis. It was suggested that miR-214 functioned as the tumor suppressor in ovarian cancer. Bioinformatic analysis indicated that miR-214 possibly regulated sema 4D by binding the sema 4D messenger RNA (mRNA) 3'-untranslated region (UTR). Sema 4D mRNA and protein levels were up-regulated in ovarian cancer tissues and SKOV-3 cells. Up-regulation of miR-214 in SKOV-3 cell line suppressed the sema 4D expression in both protein and nucleic acid levels. While, down-regulation of miR-214 in SKOV-3 cells would increase sema 4D protein and nucleic acid expression levels. The effects of miR-214 up- and down-regulation on luciferase activities of wild-type (WT) sema 4D 3'-UTR were completely removed upon introduction of mutation in 3'-UTR of WT sema 4D. Therefore, the data also demonstrated that sema 4D was the direct target of miR-214 and was negatively regulated by miR-214 in ovarian cancer cells.
Insights
MicroRNA-214 (miR-214) acts as a tumor suppressor in ovarian cancer by inhibiting cell proliferation and inducing apoptosis. It directly targets and downregulates semaphorin 4D (sema 4D) expression in cancer cells.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Ovarian cancer is a leading cause of cancer-related deaths in women.
- Aberrant expression of microRNA-214 (miR-214) and semaphorin 4D (sema 4D) is implicated in various cancers.
- Understanding the roles of miR-214 and sema 4D in ovarian cancer is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the cellular function of miR-214 in ovarian cancer.
- To determine the regulatory relationship between miR-214 and sema 4D.
- To validate sema 4D as a direct target of miR-214 in ovarian cancer cells.
Main Methods:
- Quantitative real-time PCR and Western blotting to assess miR-214 and sema 4D expression levels.
- Cell proliferation assays and apoptosis assays in SKOV-3 cells with altered miR-214 expression.
- Bioinformatic analysis to predict miR-214 binding sites on sema 4D mRNA.
- Luciferase reporter assays to confirm direct targeting of sema 4D by miR-214.
Main Results:
- miR-214 expression was significantly lower in ovarian cancer tissues and cells compared to normal controls.
- Overexpression of miR-214 inhibited SKOV-3 cell proliferation and induced apoptosis, suggesting a tumor-suppressive role.
- Sema 4D expression was upregulated in ovarian cancer tissues and cells.
- miR-214 directly targeted the 3'-untranslated region of sema 4D mRNA, suppressing its expression at both nucleic acid and protein levels.
Conclusions:
- miR-214 functions as a tumor suppressor in ovarian cancer.
- miR-214 negatively regulates sema 4D expression by directly binding to its mRNA.
- The miR-214/sema 4D axis represents a potential therapeutic target for ovarian cancer treatment.
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