Sequera Celia, Manzano Sara, Guerrero Carmen, Porras Almudena
Departamento de Bioquímica y Biología Molecular, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
Hepat Oncol. 2018 Apr 16;5(1):HEP05. doi: 10.2217/hep-2017-0026. eCollection 2018 Jan.
Rap proteins regulate liver physiopathology. For example, Rap2B promotes hepatocarcinoma (HCC) growth, while Rap1 might play a dual role. The RapGEF, Epac1, activates Rap upon cAMP binding, regulating metabolism, survival, and liver regeneration. A liver specific Epac2 isoform lacking cAMP-binding domain also activates Rap1, promoting fibrosis in alcoholic liver disease. C3G (RapGEF1) is also present in the liver, but mainly as shorter isoforms. Its function in the liver remains unknown. Information from different public genetic databases revealed that C3G mRNA levels increase in HCC, although they decrease in metastatic stages. In addition, several mutations in RapGEF1 gene are present, associated with a reduced patient survival. Based on this, C3G might represent a new HCC diagnostic and prognostic marker, and a therapeutic target.
Rap蛋白调节肝脏生理病理学。例如，Rap2B促进肝癌（HCC）生长，而Rap1可能发挥双重作用。Rap鸟嘌呤核苷酸交换因子（RapGEF）Epac1在结合cAMP后激活Rap，调节代谢、生存和肝脏再生。一种缺乏cAMP结合结构域的肝脏特异性Epac2亚型也能激活Rap1，促进酒精性肝病中的纤维化。C3G（RapGEF1）也存在于肝脏中，但主要是较短的亚型。其在肝脏中的功能尚不清楚。来自不同公共基因数据库的信息显示，C3G mRNA水平在HCC中升高，尽管在转移阶段会降低。此外，RapGEF1基因存在几种突变，与患者生存率降低相关。基于此，C3G可能代表一种新的HCC诊断和预后标志物以及治疗靶点。
