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Published on: June 9, 2023
Hsa-miR-599 inhibits breast cancer progression via BRD4/Jagged1/Notch1 axis
Yang Liu1, Ning Liu1, Danfeng Xu2
1Second Department of Ultrasonography, Hengshui People's Hospital of Hebei Province, Hengshui, China.
Abstract:
Hsa-miR-599 was identified as a tumor suppressor against cancer. This study aimed to explore possible mechanisms of antitumor effect of hsa-miR-599 against breast cancer. Tissue specimens were collected from 106 breast cancer cases, and breast cancer cell line MCF-7 was cultured for in vitro experiments. The expression pattern of hsa-miR-599 was measured via quantitative real-time polymerase chain reaction. Lipofectamine® 2000 reagent was used for cell transfection. Cell viability, motility and apoptosis were detected using MTT assay, transwell assay, and flow cytometer, respectively. Protein analysis was performed via western blot. Hsa-miR-599 expression was decreased in breast cancer tissues and cells. Moreover, its expression was negatively correlated with TNM stage (p = 0.004) and lymph node metastasis (p = 0.001). Enhanced hsa-miR-599 expression in breast cancer cells could induce the inhibition against cell proliferation, migration and invasion, and strengthen cell apoptosis. BRD4 might be a target of hsa-miR-599. Hsa-miR-599 combined with BRD4 inhibited breast cancer progression through targeting Jagged1/Notch1 pathway. Hsa-miR-599 expression is downregulated in breast cancer. Hsa-miR-599 may inactivate BRD4/Jagged1/Notch1 axis, thus suppressing malignant progression of breast cancer.
Insights
Hsa-miR-599 acts as a tumor suppressor in breast cancer by inhibiting cell proliferation and metastasis. Restoring its expression may offer a therapeutic strategy against this disease.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Hsa-miR-599 is recognized as a tumor suppressor.
- Its specific mechanisms in breast cancer require further elucidation.
Purpose of the Study:
- To investigate the antitumor mechanisms of hsa-miR-599 in breast cancer.
- To explore the correlation between hsa-miR-599 expression and clinical parameters.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) for expression analysis.
- In vitro assays including MTT, Transwell, and flow cytometry for cell behavior.
- Western blot for protein analysis.
- Cell transfection using Lipofectamine® 2000.
Main Results:
- Hsa-miR-599 expression was significantly decreased in breast cancer tissues and cells.
- Lower hsa-miR-599 levels correlated with advanced TNM stage and lymph node metastasis.
- Upregulating hsa-miR-599 suppressed proliferation, migration, and invasion while promoting apoptosis in breast cancer cells.
- Hsa-miR-599 targets BRD4, inhibiting the BRD4/Jagged1/Notch1 pathway and thus breast cancer progression.
Conclusions:
- Hsa-miR-599 exhibits significant tumor-suppressive functions in breast cancer.
- Its downregulation is linked to disease progression.
- Targeting the hsa-miR-599/BRD4/Jagged1/Notch1 axis presents a potential therapeutic avenue for breast cancer.
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