Silencing of Rab3D suppresses the proliferation and invasion of esophageal squamous cell carcinoma cells
Silencing of Rab3D suppresses the proliferation and invasion of esophageal squamous cell carcinoma cells
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DOI：
10.1016/j.biopha.2017.04.010
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发表时间：
2017-07-01
影响因子：
7.5
通讯作者：
Sun, Liangzhang
中科院分区：
文献类型：
--
作者：
Zhang, Jin;Kong, Ranran;Sun, Liangzhang
Rab 3D是ras相关GTP结合蛋白Rab家族的成员，在几种类型的癌症中被发现上调。然而，Rab 3D在食管鳞状细胞癌（ESCC）发生发展中的作用知之甚少。因此，在这项研究中，我们研究了Rab 3D在人ESCC中的表达模式和功能作用。我们证明Rab 3D在人ESCC细胞系中高度表达。此外，Rab 3D基因的敲低可显著抑制ESCC细胞的增殖，降低体内成瘤率。此外，Rab 3D基因的敲低可显著抑制ESCC细胞的迁移/侵袭，并提示EMT相关标志物的表达，包括E-cadherin的上调和N-cadherin的下调。最后，Rab 3D的敲低抑制ECA-109细胞中p-PI 3 K和p-Akt的水平。总之，我们的数据表明Rab 3D在ESCC中作为癌基因发挥作用，Rab 3D的敲低可能通过PI 3 K/Akt信号通路抑制ESCC细胞的增殖和侵袭。总的来说，这些发现表明，靶向Rab 3D可能是治疗ESCC的潜在治疗靶点。(C)2017 Elsevier Masson SAS。All rights reserved.
Rab3D is a member of the ras-related GTP-binding protein Rab family and was found up-regulated in several types of cancer. However, little is known about the role of Rab3D in carcinogenesis and progression of esophageal squamous cell carcinoma (ESCC). Thus, in this study, we investigated the expression patterns and functional roles of Rab3D in human ESCC. We demonstrated that Rab3D was highly expressed in human ESCC cell lines. In addition, knockdown of Rab3D significantly inhibited the proliferation of ESCC cells and reduced the tumorigenesis in vivo. Moreover, knockdown of Rab3D significantly suppressed ESCC cell migration/invasion and accordingly alerted EMT related markers, which including up-regulated E-cadherin and down-regulated N-cadherin in ESCC cells. Finally, knockdown of Rab3D inhibited the levels of p-PI3K and p-Akt in ECA-109 cells. In conclusion, our data demonstrated that Rab3D functions as an oncogene in ESCC and knockdown of Rab3D suppressed ESCC cell proliferation and invasion, potentially through the PI3K/Akt signaling pathway. Overall, these findings suggest that targeting the Rab3D may be a potential therapeutic target for treatment of ESCC. (C) 2017 Elsevier Masson SAS. All rights reserved.