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.

MicroRNA‑9 enhances sensitivity to cetuximab in epithelial phenotype hepatocellular carcinoma cells through regulation of the eukaryotic translation initiation factor 5A‑2

“…Accumulating evidence has demonstrated upregulated expression of eIF-5A-2 in a number of cancer types, such as bladder cancer, hepatocellular carcinoma and colon cancer ( 35 – 37 ). Inhibition of eIF-5A-2 may decrease invasion and metastasis, and enhance the therapeutic efficacy of drugs in HCC cells ( 38 , 39 ). Cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody that targets the extracellular domain of EGFR, is used to treat several cancer types ( 40 ); for example, it is used for the treatment of patients with colorectal cancer and squamous cell carcinoma of the head and neck ( 41 , 42 ).…”

Eukaryotic translation initiation factor 5A in the pathogenesis of cancers (Review)

“…Tang et al ( 49 ) reported that EIF5A2 mRNA expression was significantly increased in HCC tissues compared with nontumorous tissues; furthermore, metastatic or venous infiltrated HCC tissues showed significantly increased eIF5A2 expression compared with the HCC tissues without metastasis or venous infiltration. In addition, eIF5A2 overexpression was significantly associated with shorter survival time in patients with HCC ( 15 , 50 ). Although eIF5A1 mRNA was expressed in HCC and non-tumor tissues, eIF5A1 expression is positively correlated to the number of metastatic nodules in HCC ( 51 ).…”

Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis

“…Extensive studies have demonstrated that EIF5A2 participates in the proliferation, migration, invasion and chemotherapeutic resistance of hepatocellular carcinoma, esophageal cancer, gastric cancer, melanoma, etc. [20][21][22][23]. We proved that miR-125b-5p exerts anti-cancer effects in melanoma by targeting EIF5A2.…”