Guo Bo, Wang Wenjing, Zhao Zhenghao, Li Qian, Zhou Kaiyue, Zhao Lingyu, Wang Lumin, Yang Juan, Huang Chen
Department of cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, P. R. China.
Department of Hepatobiliary Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, P. R. China.
PLoS One. 2017 Jan 20;12(1):e0170620. doi: 10.1371/journal.pone.0170620. eCollection 2017.
Rab14 is a member of RAS oncogene family, and its dysfunction has been reported to be involved in various types of human cancer. However, its expression and function were still unclear in gastric cancer. The aim of this study was to investigate the function and mechanism of Rab14 in gastric cancer cell lines. Quantitative real-time PCR (qRT-PCR) was performed in 17 gastric adenocarcinoma tissues and 4 cell lines to detect the expression of Rab14. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT), colony formation and flow cytometry assays were employed to determine the proliferative ability, cell cycle transition and apoptosis in vitro in BGC-823 or SGC-7901 cells. Western blot was performed to investigate the pathways and mechanism of Rab14 regulation. In this study, we show that Rab14 presents a significant up-regulated expression among the paired tissue samples and cell lines in gastric cancer. When we overexpressed Rab14 in SGC-7901 cells or silenced Rab14 in BGC-823 cells, we found that Rab14 could modify cell growth, cell cycle or apoptosis, which accompanied with an obvious regulation of CCND1, CDK2 and BAX involving in AKT signaling pathway. In conclusion, this study provides a new evidence on that Rab14 functions as a novel tumor oncogene and could be a potential therapeutic target in gastric cancer.
Rab14是RAS癌基因家族的成员，据报道其功能异常与多种人类癌症有关。然而，其在胃癌中的表达和功能仍不清楚。本研究的目的是探讨Rab14在胃癌细胞系中的功能和机制。对17例胃腺癌组织和4种细胞系进行定量实时PCR（qRT-PCR）检测Rab14的表达。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）、集落形成和流式细胞术检测BGC-823或SGC-7901细胞的体外增殖能力、细胞周期转变和凋亡情况。通过蛋白质免疫印迹法研究Rab14调控的途径和机制。在本研究中，我们发现Rab14在胃癌的配对组织样本和细胞系中呈现显著上调表达。当我们在SGC-7901细胞中过表达Rab14或在BGC-823细胞中沉默Rab14时，我们发现Rab14可以改变细胞生长、细胞周期或凋亡，这伴随着细胞周期蛋白D1（CCND1）、细胞周期蛋白依赖性激酶2（CDK2）和参与AKT信号通路的 Bax 的明显调节。总之，本研究为Rab14作为一种新型肿瘤癌基因发挥作用并可能成为胃癌潜在治疗靶点提供了新的证据。
