Eukaryotic Translation Initiation Factor 5A2 (eIF5A2) Stimulates The Migration And Invasion Of Hepatocellular Carcinoma Cells Via Pathways Involving Reactive Oxygen Species

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with high morbidity and mortality rates worldwide, especially in the developing countries of East Asia. It is responsible for more than 600,000 deaths annually and about 750,000 new cases are diagnosed every year. Eukaryotic translation initiation factor 5A2 (eIF5A2) was identified as a critical gene in tumor metastasis. Research has suggested that reactive oxygen species (ROS) might serve as signaling molecules in cancer cell proliferation and migration. However, the underlying mechanisms between eIF5A2 and ROS are not fully understood. Here, we investigated the effects of ROS on eIF5A2-regulated epithelial-mesenchymal transition (EMT) and migration in six hepatocellular carcinoma (HCC) cell lines. Western hybridization, siRNA transfection, transwell migration assay, wound-healing experiment and immunofluorescence analysis were used. The protein levels of eIF5A2 in tumor tissues and adjacent tissues of 90 HCC patients with detailed clinical, pathological, and clinical follow-up data were evaluated. Overexpression of eIF5A2 was observed in cancerous tissues compared with tumor adjacent groups. 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 in HCC cells. Interestingly, N1-guanyl-1,7-diaminoheptane (GC7) could suppress the intracellular levels of ROS. After blocking EMT, administration of GC7 or N-Acetyl-L-cysteine (NAC) could not reduce cell migration further. Based on the experimental data, we concluded that inhibition of eIF5A2 might alter EMT progress to decrease the invasion and metastasis of HCC cells via ROS related pathways, eIF5A2 and ROS may become potential predictive indicators for invasion and metastasis.