Down-regulation of miR-203 induced by Helicobacter pylori infection promotes the proliferation and invasion of gastric cancer by targeting CASK.
Down-regulation of miR-203 induced by Helicobacter pylori infection promotes the proliferation and invasion of gastric cancer by targeting CASK.
复制标题
幽门螺杆菌感染诱导的miR-203下调通过靶向CASK促进胃癌的增殖和侵袭。
DOI：
10.18632/oncotarget.2600
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发表时间：
2014-11-30
期刊：
影响因子：
--
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Zhou X;Xu G;Yin C;Jin W;Zhang G
几种 microRNA (miRNA) 与幽门螺杆菌相关的胃癌 (GC) 有关。然而，miRNA在GC中的分子机制尚未完全清楚。在这项研究中，我们报道了 miR-203 在幽门螺杆菌阳性组织和细胞以及肿瘤组织中显着下调，并产生重要的功能后果。 miR-203 的异位表达显着抑制细胞增殖和侵袭。我们发现 miR-203 强烈降低 GC 细胞中 CASK 癌基因的表达。与恢复 miR-203 表达类似，CASK 下调抑制细胞生长和侵袭，而 CASK 过表达则挽救了 miR-203 的抑制作用。这些结果也可以在裸鼠身上找到。在临床标本中，CASK在肿瘤和幽门螺杆菌阳性组织中过表达，其mRNA水平与miR-203表达量呈负相关。综上所述，我们的结果表明，miR-203 在幽门螺杆菌相关的 GC 中起到生长抑制 miRNA 的作用，并且其抑制作用主要通过抑制 CASK 表达来介导。
Several microRNAs (miRNA) have been implicated in H. pylori related gastric cancer (GC). However, the molecular mechanism of miRNAs in GC has not been fully understood. In this study, we reported that miR-203 is significantly down-regulated in H. pylori positive tissues and cells and in tumor tissues with important functional consequences. Ectopic expression of miR-203 dramatically suppressed cell proliferation and invasion. We found that miR-203 strongly reduced the expression of CASK oncogene in GC cells. Similar to the restoring miR-203 expression, CASK down-regulation inhibited cell growth and invasion, whereas CASK over-expression rescued the suppressive effect of miR-203. These results can also be found in nude mice. In clinical specimens, CASK was over-expressed in tumors and H. pylori positive tissues and its mRNA levels were inversely correlated with miR-203 expression. Taken together, our results indicated that miR-203 functions as a growth-suppressive miRNA in H. pylori related GC, and that its suppressive effects are mediated mainly by repressing CASK expression.
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