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

Abstract

BackgroundTranslation 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/MethodsImmunohistochemistry 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.ResultsIn 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.ConclusionsUnveiling the mechanisms of EIF3 action in tumorigenesis may help identify attractive targets for cancer therapy.

Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells

“…eIFs have been found to be aberrantly expressed in several human tumours [16]. As one of the most important initiation factors, eIF3 plays vital roles in translation initiation [17], as well as tumorigenesis and cell proliferation [18,19]. However, there is currently little to no research regarding the role of eIF3c in ovarian cancer.…”

Impact of Eukaryotic Translation Initiation Factors on Breast Cancer: Still Much to Investigate

“…This might provide a rational for new therapies for ER-positive BC [37]. Moreover, decreased eIF3c can also suppress proliferation and stimulate apoptosis in BC cell line via the mTOR pathway [38] (Figure 2).…”

“…mTORC1 pathway could be activated by estrogen, and enhances the binding of eIF3 to the EIF4F complex [37]. Decreased eIF3c can suppress the proliferation, and can lead to apoptosis via the mTOR pathway [38]. An overexpression of eIF3h leads to an increase in protein synthesis [39].…”

Cyclovirobuxine D inhibits cell proliferation and migration and induces apoptosis in human glioblastoma multiforme and low‑grade glioma

“…Therefore, although several novel drugs have been successfully applied in the treatment of various types of tumors their efficacy is considerably low in brain tumors, notably in GBM and LGG. The antitumor effect of CVB-D has been investigated in breast and gastric cancers (13,16). However, it is uncertain whether it is effective in the treatment of GBM and LGG.…”