Li Yuanyuan, Jia Qingzhu, Wang Yu, Li Fei, Jia Zhengcai, Wan Ying
Biomedical Analysis Center, Third Military Medical University, Chongqing, China,
Med Oncol. 2015 Apr;32(4):126. doi: 10.1007/s12032-015-0562-6. Epub 2015 Mar 20.
Gastric cancer (GC) is the fourth most common cancer worldwide and is associated with a low 5-year survival rate of <24 % due to the tendency of early invasion and metastasis. Rab GTPases, which are master regulators of intracellular trafficking, have been shown to a play new role in the control of multiple tumor-related processes, including cell migration, invasion, proliferation, communication, and drug resistance. Here, we analyzed the mRNA expression levels of 63 Rab GTPases in samples from GC patients. Our data demonstrated that the expression level of Rab40b was significantly correlated with GC invasion classification (P < 0.01), lymph node metastasis (P < 0.01), and pathological stage (P < 0.01). High Rab40b mRNA expression was also correlated with shorter overall survival in patients with GC (P < 0.05). Moreover, knockdown of Rab40b protein reduced the migration and invasion of GC cells, while overexpression of Rab40b significantly promoted GC cell metastasis in nude mice. Our results also showed that Rab40b is a target gene of miR-204 and further demonstrated that Rab40b is negatively correlated with miR-204 in GC tissues. These findings indicate that Rab40b might be a novel prognostic marker and a candidate biological therapeutic target for GC.
胃癌(GC)是全球第四大常见癌症,由于其早期侵袭和转移的倾向,5年生存率较低,低于24%。Rab GTPases是细胞内运输的主要调节因子,已被证明在控制多种肿瘤相关过程中发挥新作用,包括细胞迁移、侵袭、增殖、通讯和耐药性。在此,我们分析了GC患者样本中63种Rab GTPases的mRNA表达水平。我们的数据表明,Rab40b的表达水平与GC侵袭分级(P < 0.01)、淋巴结转移(P < 0.01)和病理分期(P < 0.01)显著相关。Rab40b mRNA高表达也与GC患者较短的总生存期相关(P < 0.05)。此外,敲低Rab40b蛋白可降低GC细胞的迁移和侵袭,而Rab40b的过表达显著促进裸鼠体内GC细胞转移。我们的结果还表明,Rab40b是miR-204的靶基因,并进一步证明在GC组织中Rab40b与miR-204呈负相关。这些发现表明,Rab40b可能是GC的一种新型预后标志物和候选生物治疗靶点。