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30 August 2017 : Clinical Research  

Decreasing Eukaryotic Initiation Factor 3C (EIF3C) Suppresses Proliferation and Stimulates Apoptosis in Breast Cancer Cell Lines Through Mammalian Target of Rapamycin (mTOR) Pathway

Weipeng Zhao1ABC, Xichuan Li2B, Jun Wang3F, Chen Wang1FG, Yongsheng Jia1G, Shunzong Yuan4A, Yong Huang5D, Yehui Shi1B, Zhongsheng Tong1A*

DOI: 10.12659/MSM.906389

Med Sci Monit 2017; 23:4182-4191

Abstract

BACKGROUND: Translation initiation is the rate limiting step of protein synthesis and is highly regulated. Eukaryotic initiation factor 3C (EIF3C), an oncogene overexpressed in several human cancers, plays an important role in tumorigenesis and cell proliferation.

MATERIAL AND METHODS: Immunohistochemistry was used to determine the expression of EIF3C in breast cancer tissues from 42 patients. We investigated whether EIF3C silencing decreases breast cancer cell proliferation as assessed by colony formation assay, and whether EIF3C gene knockdown induces apoptosis as assessed by flow cytometry analysis. We utilized the stress and apoptosis signaling antibody array kit, while p-ERK1/2, p-Akt, p-Smad2, p-p38 MAPK, cleaved caspase-3, and cleaved caspase-7 were explored between EIF3C-siRNA and controls. Furthermore, the effects of EIF3C gene knockdown in mTOR pathway were analyzed by western blotting for different cell lines.

RESULTS: In EIF3C-positive tumors, 32 out of 42 showed significantly higher frequencies of high grade group by immunoreactivity (p=0.0016). BrdU incorporation after four days of cell plating was significantly suppressed in MDA-MB-231 cells by EIF3C knockdown compared with controls, with average changes of 7.8-fold (p<0.01). Clone number was significantly suppressed in MDA-MB-231 cells by EIF3C knockdown compared with controls (p<0.05). Cell apoptosis was significantly increased in the EIF3C-siRNA group when compared with the cells that were transfected with scrambled siRNA (3.51±0.0842 versus 13.24±0.2307, p<0.01). The mTOR signaling pathway was involved in decreasing EIF3C translational efficiency.

CONCLUSIONS: Unveiling the mechanisms of EIF3 action in tumorigenesis may help identify attractive targets for cancer therapy.

Keywords: Eukaryotic Initiation Factor-3

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01 November 2024 : Editorial  

Editorial: Artificial Intelligence (AI), Digital Image Analysis, and the Future of Cancer Diagnosis and Prognosis

Dinah V. Parums

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Med Sci Monit 2024; 30:e947038

0:00

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750