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Published on: June 3, 2016
The mechanisms involved in miR-9 regulated apoptosis in cervical cancer by targeting FOXO3
Haiyan Zhang1, Zhen Zhang2, Surong Wang3
1Department of Gynecology, Affiliated Qilu Hospital of Shandong University, Jinan 250012, Shandong, China; Department of Gynecology Ward-1, Linyi City People'S Hospital, Linyi 276000, Shandong, China.
Abstract:
As a seriously global health problem, cervical cancer is a great risk to women which threatens their lives. Approximately 30% patients who received definitive treatment may fail to recover from this disease. Accordingly, there is an imperatively need to explore alternative therapeutic approaches for this disease. Several studies have revealed that miR-9 was a critical regulator during cervical cancer growth. Here, we reported that the miR-9 was overexpressed in cervical tumor tissue and exerted a promoting effect on human cervical cancer cell (SiHa) growth. Both in vitro and in vivo experiments confirmed that miR-9 could stimulate the proliferation and migration of SiHa cells. In contrast, inhibition of miR-9 induced apoptosis in SiHa cells. In addition, dual luciferase reporter system assay verified that there was a strong target relationship between miR-9 and FOXO3. Result of western blot assay showed that the inhibition of miR-9 increased the expression of FOXO3. Moreover, miR-9 regulated FOXO3 downstream proteins Bax, Bcl-2 and p-Akt expressions, which suggesting that miR-9 was involved in the SiHa cells apoptosis. In conclusion, our results suggest that the inhibition of miR-9 could induce apoptosis in cervical cancer by targeting FOXO3 and presented a potential molecular target for the treatment of cervical cancer patients.
Insights
Inhibiting microRNA-9 (miR-9) shows promise for treating cervical cancer by inducing cancer cell death. This study reveals miR-9 promotes tumor growth and migration, making its inhibition a potential therapeutic strategy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Cervical cancer poses a significant global health threat to women.
- Treatment failure affects approximately 30% of patients, necessitating novel therapeutic strategies.
- MicroRNA-9 (miR-9) has been identified as a key regulator in cervical cancer progression.
Purpose of the Study:
- To investigate the role of miR-9 in human cervical cancer cell (SiHa) growth and identify its therapeutic potential.
- To elucidate the molecular mechanisms underlying miR-9's function in cervical cancer.
Main Methods:
- Overexpression and inhibition of miR-9 in SiHa cells.
- In vitro and in vivo assays to assess cell proliferation, migration, and apoptosis.
- Dual luciferase reporter assay to confirm miR-9's target relationship with FOXO3.
- Western blot analysis to evaluate protein expression levels (FOXO3, Bax, Bcl-2, p-Akt).
Main Results:
- miR-9 was found to be overexpressed in cervical tumor tissues and promoted SiHa cell proliferation and migration.
- Inhibition of miR-9 led to increased apoptosis in SiHa cells.
- FOXO3 was confirmed as a direct target of miR-9, with miR-9 inhibition upregulating FOXO3 expression.
- miR-9 influenced the expression of downstream apoptosis-related proteins (Bax, Bcl-2, p-Akt).
Conclusions:
- miR-9 plays a crucial role in promoting cervical cancer cell growth and survival.
- Targeting miR-9, specifically through its interaction with FOXO3, induces apoptosis in cervical cancer cells.
- Inhibition of miR-9 represents a potential molecular therapeutic strategy for cervical cancer treatment.
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