Knockdown of eIF3d inhibits cell proliferation through G2/M phase arrest in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains the leading cause of cancer-related death worldwide. Eukaryotic translation initiation factor 3, subunit d (eIF3d) has been recognized recently in several human cancers. In this paper, we attempt to evaluate the functional role of eIF3d in NSCLC cells. Lentivirus-mediated RNA interference (RNAi) was applied to silence eIF3d in the human NSCLC cell lines A549 and 95D. Cell viability was measured by MTT. Cell colony-forming ability was measured by colony formation. Cell cycle progression was determined by propidium iodide staining and flow cytometry. Intracellular signaling molecules were detected using a PathScan(®) intracellular signaling array kit. In this study, we firstly proved that lentivirus-mediated RNAi specifically suppressed the expression of eIF3d both at the mRNA and protein levels in A549 and 95D cell lines. Further investigations revealed that eIF3d knockdown significantly inhibited cell proliferation and colony formation. Moreover, the cell cycle of A549 cells was arrested at G2/M phase after eIF3d knockdown. Furthermore, the activations of AKT, HSP27 and SAPK/JNK were suppressed by eIF3d knockdown. This study highlights the crucial role of eIF3d in promoting NSCLC cell proliferation, and provides a foundation for further study into the clinical potential of lentiviral-mediated delivery of eIF3d RNAi therapy for treatment of NSCLC.

Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention

“…These findings are novel in the field of BC and demonstrate for the first time that EIF3D may promote the progression of this malignancy. Similarly with our findings, EIF3D was found to be up-regulated in recent studies in other cancer types including prostate cancer [ 89 ], non-small cell lung cancer [ 90 ], colon cancer [ 91 ], breast cancer [ 92 ], renal cell carcinomas [ 93 ], melanomas [ 94 ] and gliomas [ 95 ]. In the aforementioned studies, it was reported that the depletion of EIF3D resulted in cell cycle arrest and reduced the proliferation rate and colony forming ability of the cancer cells.…”

EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling

“…To further explore the biological function of EIF3D in CCRCC, shRNA was used to knockdown the expression of EIF3D in CCRCC cell lines, 786-O and ACHN cells. Functional analysis indicated that knockdown of EIF3D observably inhibited the capacity of cell proliferation and colony formation, which is in agreement with the effect of EIF3D-silencing observed in prostate cancer, glioma, melanoma, colon cancer and nSCLC cells (9)(10)(11)(12)(13). These results implied that EIF3D is a potential proto-oncogene, participating in malignant transformation of RCC.…”

“…In addition, increased eIF3e expression was reported to be associated with colon tumor development and poor prognosis, whereas knockdown of eIF3e inhibited the proliferation of colon cancer cells (8). EIF3D, one of the core subunits of eIF3, was reported to play an oncogenic role in prostate cancer, glioma, melanoma, colon cancer and nonsmall cell lung cancer (nSCLC) (9)(10)(11)(12)(13). however, the clinical significance and biological function of eIF3 in human RCC remains unclear.…”

Role of Eukaryotic Initiation Factors during Cellular Stress and Cancer Progression

“…eIF3d knockdown in NSCLC cells resulted in decreased phosphorylation and thus inhibition of AKT, HSP27, and SAPK/JNK (involved in cellular growth and cancer progression pathways). This data supports the crucial role of eIF3d in cell proliferation and cancer growth [104,105].…”