Taniguchi Kohei, Iwatsuki Ayako, Sugito Nobuhiko, Shinohara Haruka, Kuranaga Yuki, Oshikawa Yuki, Tajirika Toshihiro, Futamura Manabu, Yoshida Kazuhiro, Uchiyama Kazuhisa, Akao Yukihiro
Department of General and Gastroenterological Surgery, Osaka Medical College, Osaka, Takatsuki, Japan.
United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan.
Mol Carcinog. 2018 May;57(5):579-589. doi: 10.1002/mc.22781. Epub 2018 Jan 30.
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.
人类DEAD盒RNA解旋酶基因DDX6是从B细胞淋巴瘤细胞系RC-K8中克隆出来的。此前，我们报道过DDX6在几种癌症中作为癌基因发挥作用，比如结直肠癌和肝细胞癌。然而，DDX6在致癌过程中的详细作用机制很大程度上尚不清楚。在本研究中，我们检测了DDX6在临床胃癌（GC）样本和GC细胞中的功能。在25个临床GC样本中，癌样本的DDX6蛋白表达水平高于相邻正常组织（中位数：高1.4倍）。此外，RNA免疫沉淀分析（RIP分析）结果显示DDX6与c-Myc mRNA相关。而且，DDX6的强制过表达促进了GC细胞中c-Myc的mRNA和蛋白表达。另一方面，在二维或三维培养的GC细胞中，DDX6的基因沉默通过下调c-Myc诱导生长抑制。此外，在DDX6上调的GC临床样本中，癌样本的c-Myc mRNA表达水平高于相邻正常组织。我们在本研究中的发现表明，DDX6在GC细胞中通过与c-Myc的mRNA结合促进c-Myc表达而作为癌基因发挥作用。
