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miR-29a suppresses MCF-7 cell growth by downregulating tumor necrosis factor receptor 1
Yiling Zhao1, Fenghua Yang2, Wenyuan Li3
11 Department of Ultrasound, The Affiliated Hongqi Hospital of Mudanjiang Medical University, Mudanjiang, China.
Abstract:
Tumor necrosis factor receptor 1 is the main receptor mediating many tumor necrosis factor-alpha-induced cellular events. Some studies have shown that tumor necrosis factor receptor 1 promotes tumorigenesis by activating nuclear factor-kappa B signaling pathway, while other studies have confirmed that tumor necrosis factor receptor 1 plays an inhibitory role in tumors growth by inducing apoptosis in breast cancer. Therefore, the function of tumor necrosis factor receptor 1 in breast cancer requires clarification. In this study, we first found that tumor necrosis factor receptor 1 was significantly increased in human breast cancer tissues and cell lines, and knockdown of tumor necrosis factor receptor 1 by small interfering RNA inhibited cell proliferation by arresting the cell cycle and inducing apoptosis. In addition, miR-29a was predicted as a regulator of tumor necrosis factor receptor 1 by TargetScan and was shown to be inversely correlated with tumor necrosis factor receptor 1 expression in human breast cancer tissues and cell lines. Luciferase reporter assay further confirmed that miR-29a negatively regulated tumor necrosis factor receptor 1 expression by binding to the 3' untranslated region. In our functional study, miR-29a overexpression remarkably suppressed cell proliferation and colony formation, arrested the cell cycle, and induced apoptosis in MCF-7 cell. Furthermore, in combination with tumor necrosis factor receptor 1 transfection, miR-29a significantly reversed the oncogenic role caused by tumor necrosis factor receptor 1 in MCF-7 cell. In addition, we demonstrated that miR-29a suppressed MCF-7 cell growth by inactivating the nuclear factor-kappa B signaling pathway and by decreasing cyclinD1 and Bcl-2/Bax protein levels. Taken together, our results suggest that miR-29a is an important regulator of tumor necrosis factor receptor 1 expression in breast cancer and functions as a tumor suppressor by targeting tumor necrosis factor receptor 1 to influence the growth of MCF-7 cell.
Insights
Tumor necrosis factor receptor 1 (TNFR1) is upregulated in breast cancer. MicroRNA-29a (miR-29a) suppresses tumor growth by targeting TNFR1, inhibiting proliferation and inducing apoptosis.
Area of Science:
- Molecular Biology
- Oncology
- Gene Regulation
Background:
- Tumor necrosis factor receptor 1 (TNFR1) has contradictory roles in breast cancer, necessitating clarification.
- Understanding TNFR1's function is crucial for developing targeted breast cancer therapies.
Purpose of the Study:
- To elucidate the role of TNFR1 in breast cancer.
- To investigate the regulatory relationship between miR-29a and TNFR1 in breast cancer cells.
Main Methods:
- Quantitative analysis of TNFR1 expression in breast cancer tissues and cell lines.
- Small interfering RNA (siRNA) mediated knockdown of TNFR1.
- Bioinformatic prediction and luciferase reporter assays to confirm miR-29a binding to TNFR1.
- Overexpression of miR-29a in MCF-7 cells.
- Western blot analysis of key signaling proteins (NF-κB, cyclinD1, Bcl-2/Bax).
Main Results:
- TNFR1 expression is significantly increased in human breast cancer.
- Knockdown of TNFR1 inhibits proliferation, arrests cell cycle, and induces apoptosis.
- miR-29a expression is inversely correlated with TNFR1 in breast cancer.
- miR-29a directly targets and downregulates TNFR1, suppressing proliferation and inducing apoptosis in MCF-7 cells.
- miR-29a counteracts the oncogenic effects of TNFR1 by inactivating the NF-κB pathway.
Conclusions:
- miR-29a acts as a tumor suppressor in breast cancer by targeting TNFR1.
- The miR-29a/TNFR1 axis influences breast cancer cell growth via the NF-κB signaling pathway.
- Targeting the miR-29a/TNFR1 interaction may offer a therapeutic strategy for breast cancer.
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