Eukaryotic translation initiation factor 3, subunit C is overexpressed and promotes cell proliferation in human glioma U-87 MG cells

Abstract

Abstract. Disrupted protein translation is prevalent in tumours. Eukaryotic translation initiation factors (eIFs) were found to play an important role in various tumours. However, the involvement of eIFs in glioma remains to be elucidated. The present study explored the expression and the role of eIF 3, subunit C (eIF3c) in human glioma. The expression of eIF3c in glioma tissues was evaluated by immunohistochemistry. The impact of eIF3c inhibition on U-87 MG was explored in vitro and in vivo by lentivirus-mediated siRNA targeting eIF3c. The results revealed that overexpression of eIF3c was present in glioma tissues. Knockdown of eIF3c significantly impaired cell proliferation and colony formation, further induced cell cycle arrest and apoptosis in the U-87 MG cell line. Furthermore, tumoursphere formation in the U-87 MG glioma xenograft model was blocked by eIF3c knockdown. The involvement of eIF3c in the tumorigenesis of glioma was confirmed, suggesting eIF3c may be a promising therapy target in human glioma.

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

“…A lentiviral system of siRNA was used to depress EIF3C expression, as previously described [ 15 ]. The targeting siRNA sequence was gtcactaaaggtctgttta designed in the website ( www.invivogen.com/sirnawizard/ ), and homologous negative control siRNA was ttctccgaacgtgtgtgtacgt.…”

“…Components of EIF3 complex are required for several steps in the initiation of protein synthesis [ 12 , 13 ]. In the past few years, it has been reported that EIF3C is essential for cell proliferation in various human tumors, such as glioma [ 14 , 15 ], hepatocellular carcinoma [ 16 ], testicular seminomas [ 17 ], meningioma [ 18 ], and colon cancer [ 19 , 20 ]. Downregulated EIF3C may result in switching off polysomes and inducing cell death due to translation depressed at the initiation stage.…”

Relevance of Translation Initiation in Diffuse Glioma Biology and its Therapeutic Potential

“…Furthermore, it was demonstrated that inhibition of eIF3C in vitro using siRNA reduces cell proliferation, decreases colony formation, increases apoptosis and promotes cell cycle arrest in U87MG cells. Finally, these authors showed that lower eIF3C expression reduces tumor growth in vivo using a glioma xenograft mouse model [75].…”

“…Unfortunately, REMBRANDT and TCGA databases on Betastasis do not encompass the expression of EIF3C (Table 1). Nevertheless, eIF3C together with other eIF3 subunits have been studied in glioma tissues, in vitro and in vivo by other research teams [74][75][76][77][78].…”

Eukaryotic translation initiation factor 3 subunit C is associated with acquired resistance to erlotinib in non-small cell lung cancer

“…Recently, it has been reported that eIF3 selectively binds to mRNA related to cell proliferation and controls their translation [30]. Importantly, eIF3c is essential for cell proliferation in various human tumors [31–37]. However, it remains to be addressed whether eIF3c is involved in the resistance to anti-cancer drugs.…”