EIF3C Promotes Lung Cancer Tumorigenesis by Regulating the APP/HSPA1A/LMNB1 Axis

Abstract

Objective. This study was designed to explore the role and mechanism of eukaryotic initiation factor 3C (EIF3C) in the proliferation and apoptosis of lung cancer cells. Methods. EIF3C expression in clinic lung cancer tissues was detected by immunohistochemistry assay. Cell transfection with lentivirus EIF3C short hairpin RNA (shRNA) was performed with Lipofectamine 2000. Cell proliferation was evaluated by Celigo and MTT assays. Caspase-3/7 activity was assessed using caspase-3/7 assay kit for cell apoptosis detection. The apoptosis rate of lung cancer cells was assessed by flow cytometry. A transplanted tumor nude-mouse model was established to clarify the role of EIF3C in lung cancer. The potential mechanism of EIF3C was explored by mRNA microarray analysis. Among the top 30 up- and downregulated mRNAs selected for RT-qPCR, 5 were chosen for western blot analysis. Results. EIF3C was abnormally overexpressed in lung cancer cell lines and tissues. Silencing EIF3C suppressed the proliferation and promoted the apoptosis of lung cancer cells. In vivo experiments using transplanted tumor nude-mouse model suggested that EIF3C promoted lung cancer tumorigenesis. Further, mRNA microarray analyses identified 189 upregulated and 83 downregulated differentially expressed mRNA between the KD and negative control groups. After validation by RT-qPCR and western blot, three downstream genes (APP, HSPA1A, and LMNB1) were confirmed. Conclusion. EIF3C overexpression may facilitate the proliferation and hamper the apoptosis of lung cancer cells by regulating the APP/HSPA1A/LMNB1 axis.