Down-regulation of miR-203 induced by Helicobacter pylori infection promotes the proliferation and invasion of gastric cancer by targeting CASK.
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.
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Xiaoying
X
Zhou
Department of Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Guifang
G
Xu
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Chengqiang
C
Yin
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Wujuan
W
Jin
Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China. First Clinical Medical College of Nanjing Medical University, Nanjing, China.
Guoxin
G
Zhang
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D051528:Guanylate Kinases / Q000378:metabolism*; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology*; D015854:Up-Regulation
C546703:MIRN203 microRNA, human; D035683:MicroRNAs; C106868:CASK kinases; D051528:Guanylate Kinases