Abstract
BackgroundFTO is known to be associated with body mass and obesity in humans and its over-expression affects the energy metabolism of cancer cells. The aim of the present study is to investigate the biological role of FTO in human bladder urothelial carcinoma.MethodsPCR and western blotting are used to measure the levels of FTO in both tissues and cell lines (5637, T24, TCCSUP) of human bladder urothelial carcinoma. Raw RNA-Sequencing reads and the corresponding clinical information for bladder urothelial carcinoma are downloaded from TCGA. Cell Counting Kit-8 and wound healing assays are used to explore the effect of FTO on proliferation and migration of bladder cancer cells.ResultsThe expression of FTO mRNA in bladder urothelial carcinoma decreases significantly compared with the normal controls from both the data of real-time PCR (p < 0.05) and TCGA (p < 0.01). Loss-of-function assays revealed that knockdown of FTO significantly promotes proliferation and migration of 5637 and T24 cells. Consistently, we found that the cisplatin-induced cytotoxicity of bladder cancer cell could be rescued by co-treatment with MA2, which was previously reported as a highly selective inhibitor of FTO, compared with the cisplatin-control group.ConclusionsThese findings suggest that down-regulation of FTO plays an oncogenic role in bladder cancer. The further exploration of regulation of FTO expression may provide us a potential therapeutic target for the treatment of bladder cancer.
Highlights
fat mass and obesity-associated protein (FTO) is known to be associated with body mass and obesity in humans and its over-expression affects the energy metabolism of cancer cells
FTO mRNA was significantly down-regulated in bladder urothelial carcinoma tissues (P = 0.0143, Fig. 1a)
Western blot analysis showed an decrease in FTO expression in bladder cancer cell lines (5637, respectively) and the cisplatin+meclofenamic acid (MA2) group (T24) and TCCSUP) compared with a normal bladder epithelial cell line (SVHUC-1) (Fig. 1b)
Summary
FTO is known to be associated with body mass and obesity in humans and its over-expression affects the energy metabolism of cancer cells. The aim of the present study is to investigate the biological role of FTO in human bladder urothelial carcinoma. The fat mass and obesity-associated protein (FTO) is known to be associated with body mass and obesity in humans and its over-expression affects the energy metabolism of cancer cells [9, 10]. FTO has been proved to play a critical oncogenic role in AML as a N6-methyladenosine RNA demethylase [13] These results propose that FTO-mediated m6A demethylation might serve as a mRNA regulatory mechanism. We intend to investigate the biological role of fat mass and obesity associated protein (FTO) in human bladder urothelial carcinoma
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