Wang Wei, Zhou Pang-Hu, Hu Wei
Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Mol Med Rep. 2016 Mar;13(3):2229-34. doi: 10.3892/mmr.2016.4789. Epub 2016 Jan 15.
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.
据报道，叉头框O4（FOXO4）是胃肠道癌症中的一种新型肿瘤抑制基因；然而，其在肾透明细胞癌（ccRCC）细胞中的作用在很大程度上仍不清楚。本研究评估了FOXO4在肾癌组织和细胞中的表达水平。此外，还研究了载体介导的FOXO4过表达对786-0和Caki-1细胞系凋亡率的影响以及Bim在此过程中的作用。结果表明，与正常组织和细胞系相比，肾癌组织和细胞系中FOXO4的蛋白质和mRNA表达水平降低。FOXO4过表达显著增加了体外ccRCC细胞的凋亡率，同时Bim、裂解的半胱天冬酶3、B细胞淋巴瘤2（Bcl-2）相关X蛋白（Bax）和细胞色素c的蛋白质表达水平增加，以及Bcl-2表达降低。值得注意的是，小干扰RNA介导的Bim敲低抑制了FOXO4过表达对786-0细胞的凋亡作用。本研究结果表明，FOXO4在ccRCC中具有抑制作用，至少部分是通过线粒体依赖性途径上调Bim诱导细胞凋亡来实现的。
