title: 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.
authors.affiliation: Department of Thoracic Surgery, Shanghai First People's Hospital, Shanghai Jiaotong University, No. 100 HaiNing Road, Shanghai, 200080, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Lin
authors.forename: Liwen
authors.initials: L
authors.lastname: Xiong
authors.forename: Qiang
authors.initials: Q
authors.lastname: Lin
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics*; D059565:G2 Phase Cell Cycle Checkpoints / Q000235:genetics*; D005822:Genetic Vectors / Q000235:genetics; D057809:HEK293 Cells; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D039621:Eukaryotic Initiation Factor-3; D055551:HSP27 Heat-Shock Proteins; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt