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The Biological Function of TUSC7/miR-1224-3p Axis in Triple-Negative Breast Cancer
Bo-Hao Zheng1,2, Zhi-Xian He3, Juan Zhang4
1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People's Republic of China.
Background:
Triple-negative breast cancers (TNBC), comprising about 20% of breast cancers, have a poor prognosis. Currently, there is no effective target therapy for TNBC. LncRNA TUSC7 has been identified as a tumor suppressor in osteosarcoma and colorectal cancer. In this study, we investigated the clinical significance and the biological function of TUSC7 in breast cancer.
Methods:
We retrospectively evaluated the expression level and clinical significance of TUSC7 in 90 paired breast cancer tissues and normal tissues. The proliferation, migration, and invasion assays were performed to investigate the biological function of TUSC7 in breast cancer. Finally, microarray, a luciferase reporter assay, and quantitative real-time polymerase chain reaction (qPCR) were used to explore the potential underlying mechanism of tumor suppressor role of TUSC7.
Results:
Low TUSC7 expression was found to be an independent prognostic factor of poor overall survival (OS) in TNBC patients. Ectopic expression of TUSC7 inhibited tumor cell growth both in vitro and in vivo. TUSC7 overexpression significantly promoted the sensitivity of MDA-MB-468 cells to paclitaxel and carboplatin. In terms of the mechanism, TUSC7 might perform its biological function through binding with miR-1224-3P and regulating its expression level. Besides, genes in cell cycle pathways, such as BUB3 (budding uninhibited by benzimidazoles 3) and TGF-ß (targeting transforming growth factor β) pathways were downregulated, and genes involved in the MAPK (mitogen-activated protein kinase) (TGFBR2, transforming growth factor-beta receptor 2), PI3K-AKT (phosphoinositide 3-kinase- AKT serine/threonine kinase 1) and NF-κB (nuclear factor-kappa B subunit) pathways were upregulated in TUSC7 knockdown MDA-MB-231 cells.
Conclusion:
The low TUSC7 expression is an independent prognostic factor of poor OS of TNBC patients. TUSC7 might inhibit breast cancer cell growth and metastasis both in vitro and vivo through binding with miR-1224-3P and regulating MAPK, PI3K/AKT, and NF-κB signaling pathways.
Insights
Low expression of long noncoding RNA TUSC7 is linked to poor survival in triple-negative breast cancer (TNBC). TUSC7 may act as a tumor suppressor by influencing cell growth, metastasis, and chemotherapy sensitivity.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Triple-negative breast cancer (TNBC) presents a significant clinical challenge due to its poor prognosis and lack of targeted therapies.
- Long noncoding RNA (lncRNA) TUSC7, previously identified as a tumor suppressor in other cancers, warrants investigation in breast cancer.
Purpose of the Study:
- To investigate the clinical significance of lncRNA TUSC7 in breast cancer.
- To elucidate the biological function and underlying molecular mechanisms of TUSC7 in TNBC.
Main Methods:
- Retrospective analysis of TUSC7 expression in 90 paired breast cancer tissues and adjacent normal tissues.
- In vitro and in vivo assays to assess the impact of TUSC7 on tumor cell proliferation, migration, and invasion.
- Mechanistic studies including microarray, luciferase reporter assays, and qPCR to explore TUSC7's regulatory pathways.
Main Results:
- Low TUSC7 expression is an independent prognostic factor for poor overall survival in TNBC patients.
- Overexpression of TUSC7 inhibited tumor growth in vitro and in vivo and enhanced sensitivity to paclitaxel and carboplatin.
- TUSC7 interacts with miR-1224-3p and influences cell cycle, MAPK, PI3K/AKT, and NF-κB signaling pathways.
Conclusions:
- Reduced TUSC7 expression serves as a prognostic marker for adverse outcomes in TNBC.
- TUSC7 exhibits tumor-suppressive functions in breast cancer, potentially through modulation of miR-1224-3p and key signaling pathways.
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