Roles of eIF3m in the tumorigenesis of triple negative breast cancer

Author:

Han Wei,Zhang Cong,Shi Chun-tao,Gao Xiao-jiao,Zhou Ming-hui,Shao Qi-xiang,Shen Xiao-jun,Wu Cheng-jiang,Cao Fang,Hu Yong-wei,Yuan Jian-liang,Ding Hou-zhong,Wang Qing-hua,Wang Hao-nanORCID

Abstract

Abstract 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.

Funder

Jiangsu University Science and Technology Program of Clinical Medicine

Wuxi Youth Projection of Health and family planning commission

Wuxi Scientific and Technological Development of Medical and Health Guidance Programs

Kunshan Major Project of Social Research and Development

Publisher

Springer Science and Business Media LLC

Subject

Cancer Research,Genetics,Oncology

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