title: Eukaryotic translation initiation factor 5A2 regulates the migration and invasion of hepatocellular carcinoma cells via pathways involving reactive oxygen species.
abstract: Eukaryotic translation initiation factor 5A2 (eIF5A2) has been identified as a critical gene in tumor metastasis. Research has suggested that reactive oxygen species (ROS) serve as signaling molecules in cancer cell proliferation and migration. However, the mechanisms linking eIF5A2 and ROS are not fully understood. Here, we investigated the effects of ROS on the eIF5A2-induced epithelial-mesenchymal transition (EMT) and migration in six hepatocellular carcinoma (HCC) cell lines. Western hybridization, siRNA transfection, transwell migration assays, wound-healing assays, and immunofluorescence analysis were used. The protein levels of eIF5A2 in tumor and adjacent tissue samples from 90 HCC patients with detailed clinical, pathological, and clinical follow-up data were evaluated. Overexpression of eIF5A2 was found in cancerous tissues compared with adjacent tissues. We found that eIF5A2 overexpression in HCC was associated with reduced overall survival. Knockdown of eIF5A2 and intracellular reduction of ROS significantly suppressed the invasion and metastasis of HCC cells. Interestingly, N1-guanyl-1, 7-diaminoheptane (GC7) suppressed the intracellular ROS levels. After blocking the EMT, administration of GC7 or N-acetyl-L-cysteine did not reduce cell migration further. Based on the experimental data, we concluded that inhibition of eIF5A2 alters progression of the EMT to decrease the invasion and metastasis of HCC cells via ROS-related pathways.
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Ya-Su
authors.initials: YS
authors.lastname: Lv
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Yue-Xiao
authors.initials: YX
authors.lastname: Tang
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Biological Chemistry, Zhejiang Chinese Medical University, Hangzhou, 310053, China.
authors.forename: Xiao-Ling
authors.initials: XL
authors.lastname: Chen
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Zheng
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Shang-Zhi
authors.initials: SZ
authors.lastname: Xie
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Multi-Organ Transplantation of Ministry of Public Health, Hangzhou, 310003, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Cell Biology and Medical Genetics, Research Center for Molecular Medicine, National Education Base for Basic Medical Sciences, Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China.
authors.forename: Xian-Ning
authors.initials: XN
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D010448:Peptide Initiation Factors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D000097574:Eukaryotic Translation Initiation Factor 5A
chemical_list: D000111:Acetylcysteine; D006147:Guanine; D010448:Peptide Initiation Factors; D016601:RNA-Binding Proteins; D017382:Reactive Oxygen Species; D000097574:Eukaryotic Translation Initiation Factor 5A; C100667:N(1)-guanyl-1,7-diaminoheptane
keywords: epithelial-mesenchymal transition; eukaryotic translation initiation factor 5A2; hepatocellular carcinoma; migration; reactive oxygen species