Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells
Oncogene RNA helicase DDX6 promotes the process of c-Myc expression in gastric cancer cells
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DOI：
10.1002/mc.22781
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发表时间：
2018-05-01
影响因子：
4.6
通讯作者：
Akao, Yukihiro
中科院分区：
文献类型：
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作者：
Taniguchi, Kohei;Iwatsuki, Ayako;Akao, Yukihiro
从B细胞淋巴瘤细胞系RC-K8中克隆了人DEAD盒RNA解旋酶基因DDX 6。以前，我们报道了DDX 6作为癌基因在几种癌症如结直肠癌和肝细胞癌中起作用。然而，DDX 6在致癌作用中的详细机制在很大程度上是未知的。在这项研究中，我们研究了DDX 6在临床胃癌（GC）样品和GC细胞中的功能。25例胃癌组织中DDX 6蛋白表达水平均高于癌旁正常组织（中位数为1.4倍）。此外，RNA免疫沉淀试验（RIP试验）的结果显示DDX 6与c-Myc mRNA相关。此外，DDX 6的强制过表达促进GC细胞中c-Myc的mRNA和蛋白表达。另一方面，DDX 6的基因沉默通过在二维或三维生长的GC细胞中下调c-Myc诱导生长抑制。DDX 6上调的胃癌组织中c-Myc mRNA表达水平高于癌旁正常组织。我们的研究结果表明，DDX 6在GC细胞中起癌基因作用，其作用机制可能是通过与c-Myc mRNA结合而促进c-Myc的表达。
Human DEAD-box RNA helicase gene DDX6 was cloned from B-cell lymphoma cell line RC-K8. Previously, we reported that DDX6 acts as oncogene in several cancers such as colorectal cancer and hepatocellular carcinoma. However, the detailed mechanism of DDX6 action in carcinogenesis is largely unknown. In this study, we examined the functions of DDX6 in clinical gastric cancer (GC) samples and GC cells. DDX6 protein expression levels of cancer samples were higher than those of the adjacent normal tissues in 25 clinical GC samples (median value: 1.4 times higher). Also, the results of an RNA immunoprecipitation-assay (RIP-assay) showed that DDX6 associated with c-Myc mRNA. Moreover, enforced overexpression of DDX6 promoted both mRNA and protein expression of c-Myc in GC cells. On the other hand, the gene silencing of DDX6 induced growth suppression through down-regulation of c-Myc in GC cells grown in either two or three dimensions. Furthermore, c-Myc mRNA expression levels of cancer samples were higher than those of the adjacent normal tissues in DDX6 up-regulated-GC clinical samples. Our findings in this study suggested that DDX6 acted as oncogene in GC cells through promotion of c-Myc expression by association with the mRNA of c-Myc.