Nicolau-Neto Pedro, Palumbo Antonio, De Martino Marco, Esposito Francesco, de Almeida Simão Tatiana, Fusco Alfredo, Nasciutti Luiz Eurico, Meireles Da Costa Nathalia, Ribeiro Pinto Luis Felipe
Programa de Carcinogênese Molecular, Instituto Nacional de Câncer-INCA, Rua Andre Cavalcanti 37, Rio de Janeiro 20231-050, RJ, Brazil.
Laboratório de Interações Celulares, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Prédio de Ciências da Saúde-Ilha do Fundão, A. Carlos Chagas, Rio de Janeiro 21941-902, RJ, Brazil.
Genes (Basel). 2018 Mar 29;9(4):188. doi: 10.3390/genes9040188.
FOXM1 (forkhead box protein M1) is a transcription factor that participates in all stages of tumor development, mainly through the control of cell cycle and proliferation, regulating the expression of genes involved in G1/S and G2/M transition and M phase progression. The ubiquitin conjugating enzyme E2 (UBE2C) is a member of the anaphase promoting complex/cyclosome, promoting the degradation of several target proteins along cell cycle progression, during metaphase/anaphase transition. FOXM1 and UBE2C have been found overexpressed in a wide range of different solid tumors. Therefore, the aim of this study was to investigate whether is a transcriptional target of FOXM1, using esophageal squamous cell carcinoma (ESCC) as a model, in addition to several cancer-deposited data. Our results show that and expression present a positive correlation in normal tissues and in 25 distinct tumor types, including ESCC, where these genes are overexpressed. Moreover, FOXM1 binds to promoter region in ESCC cell line and transcriptionally activates it, leading to UBE2C upregulation. In conclusion, this study provides evidences that FOXM1 transcriptionally regulates expression in ESCC and their deregulation may be a general phenomenon in human neoplasias.
叉头框蛋白M1(FOXM1)是一种转录因子,主要通过控制细胞周期和增殖参与肿瘤发展的各个阶段,调节参与G1/S和G2/M转换以及M期进程的基因表达。泛素结合酶E2(UBE2C)是后期促进复合体/细胞周期体的成员之一,在中期/后期转换期间,随着细胞周期进程促进几种靶蛋白的降解。FOXM1和UBE2C已被发现在多种不同的实体瘤中过表达。因此,本研究的目的是,除了一些癌症相关数据外,以食管鳞状细胞癌(ESCC)为模型,研究[此处原文缺失具体基因名称]是否为FOXM1的转录靶点。我们的结果表明,在正常组织以及包括ESCC在内的25种不同肿瘤类型中,[此处原文缺失具体基因名称]和UBE2C的表达呈正相关,这些基因在这些肿瘤中过表达。此外,FOXM1在ESCC细胞系中与[此处原文缺失具体基因名称]启动子区域结合并转录激活它,导致UBE2C上调。总之,本研究提供了证据表明FOXM1在ESCC中对[此处原文缺失具体基因名称]的表达进行转录调控,并且它们的失调可能是人类肿瘤中的普遍现象。