Du Jiang, Fu Lin, Hao Jie, Lin Xiumin, Dong Qianze
Department of Pathology, College of Basic Medical Science, China Medical University, The First Affiliated Hospital of China Medical University, Shenyang, China.
University of Central Florida College of Medicine, Burnett School of Biomedical Sciences, Orlando, FL, USA.
J Oncol. 2020 Oct 31;2020:3494396. doi: 10.1155/2020/3494396. eCollection 2020.
Dysregulation of Rab11a has been implicated in the progression of several cancers. However, there have been no such studies for human gastric cancers. In the current study, we examined Rab11a protein expression and found it was upregulated in 49 of 108 gastric cancer tissues and correlated with local invasion, nodal metastasis, and advanced stage. Rab11a protein was higher in gastric cancer cell lines than normal gastric cell line. We transfected Rab11a plasmid and siRNA in both MGC803 and AGS cell lines. Rab11a overexpression increased the cell growth rate, colony numbers, and invasion ability in both MGC803 and AGS cell lines. Downregulation of Rab11a using siRNA decreased the cell proliferation rate, colony numbers, and inhibited invasion. Rab11a overexpression also conferred cisplatin resistance. Annexin V/PI staining showed that Rab11a overexpression suppressed cisplatin-induced apoptosis, while Rab11a depletion promoted cell apoptosis. We also showed that Rab11a overexpression maintained mitochondrial membrane potential. Western blot analysis revealed that Rab11a increased protein expression of MMP2, cyclin D1, Bcl-2, p-FAK, and p-AKT, while Rab11a depletion showed the opposite effects. Blockage of FAK using inhibitor downregulated Bcl-2, cyclin D1, MMP2, and p-AKT expression and abolished the effects of Rab11a on these proteins. In summary, our data demonstrated that Rab11a is upregulated in human gastric cancers. Rab11a facilitated cell proliferation and invasion, as well as cisplatin sensitivity and mitochondrial membrane potential, possibly via the FAK/AKT signaling pathway.
Rab11a的失调与多种癌症的进展有关。然而，尚未有针对人类胃癌的此类研究。在本研究中，我们检测了Rab11a蛋白表达，发现其在108例胃癌组织中的49例中上调，并与局部侵袭、淋巴结转移和晚期相关。Rab11a蛋白在胃癌细胞系中高于正常胃细胞系。我们在MGC803和AGS细胞系中分别转染了Rab11a质粒和小干扰RNA（siRNA）。Rab11a过表达增加了MGC803和AGS细胞系的细胞生长速率、集落数量和侵袭能力。使用siRNA下调Rab11a可降低细胞增殖速率、集落数量并抑制侵袭。Rab11a过表达还赋予了顺铂抗性。膜联蛋白V/碘化丙啶（Annexin V/PI）染色显示，Rab11a过表达抑制了顺铂诱导的细胞凋亡，而Rab11a缺失则促进了细胞凋亡。我们还表明，Rab11a过表达维持了线粒体膜电位。蛋白质印迹分析显示，Rab11a增加了基质金属蛋白酶2（MMP2）、细胞周期蛋白D1、Bcl-2、磷酸化粘着斑激酶（p-FAK）和磷酸化蛋白激酶B（p-AKT）的蛋白表达，而Rab11a缺失则产生相反的效果。使用抑制剂阻断FAK可下调Bcl-2、细胞周期蛋白D1、MMP2和p-AKT的表达，并消除Rab11a对这些蛋白的影响。总之，我们的数据表明Rab11a在人类胃癌中上调。Rab11a可能通过FAK/AKT信号通路促进细胞增殖和侵袭，以及顺铂敏感性和线粒体膜电位。
