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Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
MiR-16-5p inhibits breast cancer by reducing AKT3 to restrain NF-κB pathway
1Department of Breast and Thyroid Surgery, Shaoxing People's Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000.
Abstract:
Background: Breast cancer endangers the life of women and has become the major cause of deaths among them. MiRNAs are found to exert a regulatory effect on the migration, proliferation and apoptosis of breast cancer cells. This research aims at investigating the miR-16-5p expression and its effect on the pathogenesis of breast cancer. Methods: Their clinical data were analyzed with qRT-PCR. CCK8, EdU and Transwell was performed to explore the function of miR-16-5p in cell migration and proliferation of breast cancer cells. Dual-luciferase reporter assay, immunohistochemistry and Western blotting were carried out to explore the relation between miR-16-5p and AKT3. Results: It was discovered that miR-16-5p was lowly expressed in breast cancer patients. Meanwhile, breast cancer patients with under-expressed miR-16-5p had a lower survival rate than those with highly expressed miR-16-5p. Furthermore, decreased miR-16-5p in cell and animal models enhanced migration and proliferation of breast cancer cells, stimulated cell cycle and reduced cell apoptosis. Finally, we found miR-16-5p restrained the NF-κB pathway and decreased AKT3 gene, thereby suppressing the breast cancer development. Conclusion: It can be seen that miR-16-5p exhibits a low expression in breast cancer tissues, which can inhibit breast cancer by restraining the NF-κB pathway and elevating reducing AKT3.
Insights
MicroRNA-16-5p (miR-16-5p) is downregulated in breast cancer, correlating with lower survival rates. Restoring miR-16-5p inhibits tumor growth by suppressing the NF-κB pathway and AKT3.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Breast cancer is a leading cause of death in women globally.
- MicroRNAs (miRNAs) play crucial roles in regulating breast cancer cell behavior, including migration, proliferation, and apoptosis.
- Understanding specific miRNA roles, like miR-16-5p, is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the expression levels of miR-16-5p in breast cancer.
- To determine the functional impact of miR-16-5p on breast cancer cell pathogenesis, migration, proliferation, and apoptosis.
- To elucidate the molecular mechanisms underlying miR-16-5p's role, particularly its relationship with AKT3 and the NF-κB pathway.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) for miR-16-5p expression analysis.
- Cell proliferation (CCK8, EdU) and migration (Transwell) assays.
- Dual-luciferase reporter assay, immunohistochemistry, and Western blotting to assess miR-16-5p, AKT3, and NF-κB pathway interactions.
Main Results:
- miR-16-5p was significantly downregulated in breast cancer tissues and correlated with poorer patient survival.
- Reduced miR-16-5p expression promoted breast cancer cell migration, proliferation, cell cycle progression, and inhibited apoptosis in vitro and in vivo.
- miR-16-5p was found to inhibit the NF-κB pathway and decrease AKT3 expression, thereby suppressing breast cancer development.
Conclusions:
- miR-16-5p acts as a tumor suppressor in breast cancer.
- Low miR-16-5p expression contributes to breast cancer progression.
- Targeting miR-16-5p or its downstream pathways (NF-κB, AKT3) may offer therapeutic strategies for breast cancer.
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