Ubiquitin-like protein FAT10 promotes bladder cancer progression by stabilizing survivin.

Dingxiang Dong,Ben Che,Xiaoqing Xi,Xiuxia Liu,Jun Lei,Weifan Jiang,Leifeng Chen,Jianghua Shao,Jin Ge

doi:10.18632/oncotarget.12976

Abstract

Human HLA-F adjacent transcript 10 (FAT10) is a member of the ubiquitin-like-modifier family of proteins, which have been implicated in cancer development. In addition, the Survivin protein promotes proliferation in bladder cancer (BC). In this study, we explored the link between FAT10 and Survivin. FAT10 expression was dramatically up-regulated in BC tissue samples, and Kaplan-Meier survival analysis revealed that BC patients with high FAT10 expression had shorter overall survival than those with low FAT10 expression. Moreover, RNAi-mediated FAT10 knockdown decreased Survivin protein levels and inhibited BC proliferation both in vitro and in vivo. FAT10 directly bound to and stabilized Survivin protein, thereby promoting cancer cell proliferation by inhibiting ubiquitin-mediated degradation. These results reveal a novel mechanism by which FAT10 promotes tumor proliferation by directly stabilizing Survivin protein in BC.

Highlights

Bladder cancer (BC) is the most common and most fatal type of urinary tumor [1, 2]
We examined F adjacent transcript 10 (FAT10) expression in 50 bladder cancer (BC) tissue samples and corresponding adjacent normal tissues using quantitative RT-PCR (qRT-PCR) and western blotting. qRT-PCR revealed that FAT10 mRNA expression was increased in BC tissues compared to corresponding adjacent tissues (Figure 1B), and western blots showed that FAT10 protein was overexpressed in 68% (34/50) of the BC tissue samples (Figure 1C)
These results indicate that FAT10 mRNA and protein levels are upregulated in BC tissues

Summary

Introduction

5-year survival rates in BC patients have improved, one third of all patients still experience recurrence. FAT10 is involved in various essential cellular development processes, including immune-mediated inflammation, apoptosis, cell cycle progression, and proliferation [6,7,8]. Studies have shown that FAT10 promotes tumor development and proliferation [9]. FAT10 expression is elevated in liver cancer, stomach cancer, glioma, and other cancer tissues [6, 10, 11]. We recently demonstrated that FAT10 protein is expressed in many tumor cells, and high FAT10 levels were associated with increased proliferation in hepatocellular carcinoma, colon cancer, and cervical carcinoma cells [12, 13]. The role of FAT10 expression in BC cells remains unclear

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Results

Conclusion