Overexpression of F-box and WD repeat domain containing 7 prevents tumor growth of bladder cancer cells through regulating SREBP1a.

Abstract

BackgroundThis study aimed to explore the effect of F-box and WD repeat domain containing 7 (FBXW7) overexpression on bladder cancer, and to determine the regulatory effect of FBXW7 on sterol regulatory element-binding protein 1a (SREBP1a) in bladder cancer.MethodsThe function of F-box and FBXW7 in tumor growth of bladder cancer cells was investigated using in vivo and in vitro models. We constructed and transfected FBXW7 overexpression vectors into T24 and J82 bladder cancer cells. After transfections, the expression of FBXW7 at messenger RNA (mRNA) and protein levels in human bladder cancer cells was confirmed. To verify the effect of FBXW7 on tumor growth, cell proliferation and migration were detected in the tumor cells after overexpression of FBXW7. Additionally, an in vivo tumor model was produced by inoculating the tumor cells and the effect of FBXW7 was evaluated. Finally, the regulation mechanisms were determined.ResultsOur data showed that overexpression of FBXW7 in J28 and T24 cells significantly inhibited the migration and proliferation of J82 and T24 cells, arrested the cells at G0/G1 phase, and up-regulated phosphorylation of glycogen synthase kinase-3β, while suppressing SREBP1a expression. In vivo data also showed that FBXW7 overexpression triggered apoptosis of tumor cells, prevented the pathological changes of tumor tissues, up-regulated p-GSK3β expression, and suppressed SREBP1a expression. In addition, an interaction between FBXW7 and SREBP1a was confirmed by co-immunoprecipitation.ConclusionsTogether, our data indicate that overexpression of FBXW7 prevents tumor growth of bladder cancer cells, likely through suppressing SREBP1a expression.