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Published on: May 1, 2020
Roles of eIF3m in the tumorigenesis of triple negative breast cancer
Wei Han1, Cong Zhang2, Chun-Tao Shi3
11Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan Jiangsu, 215300 People's Republic of China.
Background:
Without targets, triple negative breast cancer (TNBC) has the worst prognosis in all subtypes of breast cancer (BC). Recently, eukaryotic translation initiation factor 3 m (eIF3m) has been declared to be involved in the malignant progression of various neoplasms. The aim of this study is to explore biological functions of eIF3m in TNBC.
Methods:
Multiple databases, including Oncomine, KM-plotter and so on, were performed to analyze prognosis and function of eIF3m in TNBC. After transfection of eIF3m-shRNA lentivirus, CCK-8, colony formation assay, cell cycle analysis, wound healing assay, transwell assays, mitochondrial membrane potential assay and cell apoptosis analysis were performed to explore the roles of eIF3m in TNBC cell bio-behaviors. In addition, western blotting was conducted to analyze the potential molecular mechanisms of eIF3m.
Results:
In multiple databases, up-regulated eIF3m had lower overall survival, relapse-free survival and post progression survival in BC. EIF3m expression in TNBC was obviously higher than in non-TNBC or normal breast tissues. Its expression in TNBC was positively related to differentiation, lymph node invasion and distant metastasis. After knockdown of eIF3m, cell proliferation, migration, invasion and levels of mitochondrial membrane potential of MDA-MB-231 and MDA-MB-436 were all significantly suppressed, while apoptosis rates of them were obviously increased. In addition, eIF3m could regulate cell-cycle, epithelial-mesenchymal transition and apoptosis-related proteins. Combined with public databases and RT-qPCR, 14 genes were identified to be modulated by eIF3m in the development of TNBC.
Conclusions:
eIF3m is an unfavorable indicator of TNBC, and plays a vital role in the process of TNBC tumorigenesis.
Insights
Eukaryotic translation initiation factor 3m (eIF3m) promotes triple-negative breast cancer (TNBC) progression. Lowering eIF3m levels suppresses TNBC cell growth, migration, and invasion, indicating its role as an unfavorable prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Triple-negative breast cancer (TNBC) presents a poor prognosis due to a lack of targeted therapies.
- Eukaryotic translation initiation factor 3m (eIF3m) is implicated in the malignant progression of various cancers.
Purpose of the Study:
- To investigate the biological functions and prognostic significance of eIF3m in TNBC.
- To explore the role of eIF3m in TNBC cell proliferation, migration, invasion, and apoptosis.
Main Methods:
- Bioinformatic analysis using Oncomine and KM-plotter databases for prognosis.
- In vitro assays including CCK-8, colony formation, cell cycle, wound healing, Transwell, mitochondrial membrane potential, and apoptosis assays after eIF3m knockdown.
- Western blotting to elucidate molecular mechanisms and identify regulated genes.
Main Results:
- Elevated eIF3m expression correlates with poorer survival outcomes in breast cancer patients.
- eIF3m is significantly upregulated in TNBC tissues and associated with advanced disease features.
- Knockdown of eIF3m suppressed TNBC cell proliferation, migration, invasion, and mitochondrial potential, while increasing apoptosis.
- eIF3m influences cell cycle, epithelial-mesenchymal transition, and apoptosis-related proteins, modulating 14 key genes in TNBC development.
Conclusions:
- eIF3m serves as an unfavorable prognostic indicator for TNBC.
- eIF3m plays a critical role in TNBC tumorigenesis and progression.
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