Feng Jin, Zhao Jinpeng, Xie Haibin, Yin Yong, Luo Guanghua, Zhang Jun, Feng Yuehua, Li Zhong
Department of General Surgery, The First People's Hospital of Changzhou, the Third Affiliated Hospital of Soochow University, Changzhou, 213000, China.
Tumour Biol. 2015 May;36(5):3621-8. doi: 10.1007/s13277-014-2999-1. Epub 2015 Jan 12.
Recent studies have demonstrated that neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is highly expressed in various tumor tissues and cell lines. However, research on the role of NEDD9 in gastric cancer (GC) is rare, and the potential mechanism in tumor progression has not yet been explored. In this study, we investigated the role and mechanism of NEDD9 in GC. The expression of NEDD9 in GC tissues and cell lines was measured by immunohistochemistry, qRT-PCR, and Western blot, respectively. Inhibiting NEDD9 expression was carried out by siRNA transfection, and upregulating of NEDD9 was via NEDD9 overexpression plasmid. The ability of proliferation, migration, and invasion was detected by MTT assay, scratch wound assay, and transwell assay, respectively. The expression of vimentin, E-cadherin, Zeb1, and Zeb2 was measured by Western blot and qRT-PCR. We found that NEDD9 expression was dramatically increased both in GC tissues and cell lines, and the expression was significantly related to GC development. Knockdown of NEDD9 in SGC-7901 strongly inhibited its malignant capacity in vitro. Meanwhile, upregulation of NEDD9 in GES-1 increased the malignant capacity. In addition, the expression of vimentin, Zeb1, and Zeb2 was positively correlated with NEDD9, while E-cadherin was opposite. Collectively, our findings suggest that NEDD9 acts as an oncogene and promotes GC metastasis via EMT.
最近的研究表明,神经前体细胞表达的发育下调基因9(NEDD9)在各种肿瘤组织和细胞系中高表达。然而,关于NEDD9在胃癌(GC)中的作用的研究很少,其在肿瘤进展中的潜在机制尚未得到探索。在本研究中,我们调查了NEDD9在GC中的作用和机制。分别通过免疫组织化学、qRT-PCR和蛋白质印迹法检测GC组织和细胞系中NEDD9的表达。通过小干扰RNA(siRNA)转染抑制NEDD9表达,通过NEDD9过表达质粒上调NEDD9。分别通过MTT法、划痕试验和Transwell试验检测增殖、迁移和侵袭能力。通过蛋白质印迹法和qRT-PCR检测波形蛋白、E-钙黏蛋白、锌指蛋白1(Zeb1)和锌指蛋白2(Zeb2)的表达。我们发现,NEDD9在GC组织和细胞系中的表达均显著增加,且该表达与GC的进展显著相关。在SGC-7901细胞中敲低NEDD9可强烈抑制其体外恶性能力。同时,在GES-1细胞中上调NEDD9可增加其恶性能力。此外,波形蛋白、Zeb1和Zeb2的表达与NEDD9呈正相关,而E-钙黏蛋白则相反。总的来说,我们的研究结果表明,NEDD9作为一种癌基因,通过上皮-间质转化促进GC转移。