Down-regulation of FTO promotes proliferation and migration, and protects bladder cancer cells from cisplatin-induced cytotoxicity.
BACKGROUND
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.


METHODS
PCR 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.


RESULTS
The 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.


CONCLUSIONS
These 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.
['Wen|Lijie|L|', 'Pan|Xianwei|X|', 'Yu|Yang|Y|', 'Yang|Bo|B|']
D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO D000970:Antineoplastic Agents D002295:Carcinoma, Transitional Cell D002465:Cell Movement D049109:Cell Proliferation D002945:Cisplatin D015536:Down-Regulation D006801:Humans D014407:Tumor Cells, Cultured D001749:Urinary Bladder Neoplasms
FTO Bladder urothelial carcinoma Cisplatin Meclofenamic acid