EIF5A2 predicts outcome in localised invasive bladder cancer and promotes bladder cancer cell aggressiveness in vitro and in vivo

Abstract

Background:EIF5A2, eukaryotic translation initiation factor 5A2, is associated with several human cancers. In this study, we investigated the role of EIF5A2 in the metastatic potential of localised invasive bladder cancer (BC) and its underlying molecular mechanisms were explored.Methods:The expression pattern of EIF5A2 in localised invasive BC was determined by immunohistochemistry. In addition, the function of EIF5A2 in BC and its underlying mechanisms were elucidated with a series of in vitro and in vivo assays.Results:Overexpression of EIF5A2 was an independent predictor for poor metastasis-free survival of localised invasive BC patients treated with radical cystectomy. Knockdown of EIF5A2 inhibited BC cell migratory and invasive capacities in vitro and metastatic potential in vivo and reversed epithelial–mesenchymal transition (EMT), whereas overexpression of EIF5A2 promoted BC cells motility and invasiveness in vitro and metastatic potential in vivo and induced EMT. In addition, we found that EIF5A2 might activate TGF-β1 expression to induce EMT and drive aggressiveness in BC cells. EIF5A2 stabilized STAT3 and stimulated nuclear localisation of STAT3, which resulted in increasing enrichment of STAT3 onto TGF-β1 promoter to enhance the transcription of TGF-β1.Conclusions:EIF5A2 overexpression predicts tumour metastatic potential in patients with localised invasive BC treated with radical cystectomy. Furthermore, EIF5A2 elevated TGF-β1 expression through STAT3 to induce EMT and promotes aggressiveness in BC.

The translation factor eIF5A and human cancer

“…Its over-expression, usually visualized by IHC, has been observed in cancer of the ovary [55, 74], colorectal carcinoma [75], bladder cancer [59, 76, 77], hepatocellular carcinoma [78, 79], non-small cell lung cancer [80, 81], pancreatic cancer [66], esophageal squamous cell carcinoma [35], and gastric cancer [82]. Both eIF5A1 and eIF5A2 isoforms are present in hepatocellular [57] and pancreatic [66] cancer.…”

Evaluation of Su Fu’ning Lotion’s Inhibitory Effects on Bladder Cancer Cells In Vitro and In Vivo by Intravesical Instillation

“…21 The BIU-87 cells were usually inoculated subcutaneously to generate the bladder tumor animal model. 22 The doubling time of BUI-87 cell population (22nd generation) was 34 hours.…”

Knockdown of EIF5A2 inhibits the malignant potential of non-small cell lung cancer cells

“…EIF5A2 has been implicated in a number of cancers, including bladder cancer, colorectal cancer, pancreatic adenocarcinoma, esophageal squamous cell carcinoma, gastric adenocarcinoma, breast cancer, prostate adenocarcinoma, hepatocellular carcinoma, ovarian cancer and melanoma (9,(14)(15)(16)(17)(18)(19)(20)(21)(22). Patients with esophageal squamous cell carcinoma, bladder cancer and pancreatic adenocarcinoma in which EIF5A2 is overexpressed have been demonstrated to exhibit statistically significantly shorter survival times (14,17,20).…”

“…Patients with esophageal squamous cell carcinoma, bladder cancer and pancreatic adenocarcinoma in which EIF5A2 is overexpressed have been demonstrated to exhibit statistically significantly shorter survival times (14,17,20). Furthermore, patients with hepatocellular carcinoma in which EIF5A2 is overexpressed have a greater number of metastases and are more likely to present with venous invasion (23,24).…”

“…MicroRNA-30b (miR-30b) and miR-125b have been demonstrated to suppress gastric adenocarcinoma cells and hepatocellular carcinoma cells respectively via their direct inhibitory effects on EIF5A2 translation (20,22). Therefore, any compound that increases miR-30b and/or miR-125b transcription has the potential to serve as a successful therapy for NSCLC.…”