Overexpression of FOXO4 induces apoptosis of clear-cell renal carcinoma cells through downregulation of Bim

Abstract

Forkhead box O4 (FOXO4) has been reported to be a novel tumor suppressor gene in gastrointestinal cancers; however, its role in clear-cell renal carcinoma cells (ccRCC) has remained largely elusive. The present study assessed the expression levels of FOXO4 in RCC tissues and cells. Furthermore, the effects of vector-mediated overexpression of FOXO4 on the apoptotic rate of the 786-0 and Caki-1 cell lines and the role of Bim in this process were investigated. The results demonstrated that the protein and mRNA expression levels of FOXO4 were decreased in renal cancer tissues and cell lines compared with those in normal tissues and cell lines. FOXO4 overexpression significantly increased the apoptotic rate of ccRCC cells in vitro, along with increased protein expression levels of Bim, cleaved-caspase 3, B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax) and cytochrome c, as well as a decrease in Bcl-2 expression. Of note, the apoptotic effects of FOXO4 overexpression in 786-0 cells were inhibited by small interfering RNA-mediated knockdown of Bim. The results of the present study indicated that FOXO4 has an inhibitory effect in ccRCC, at least in part through inducing apoptosis via upregulation of Bim in the mitochondria-dependent pathway.