MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor.

• Main Authors: Jun Tie, Yanglin Pan, Lina Zhao, Kaichun Wu, Jie Liu, Shiren Sun, Xuegang Guo, Biaoluo Wang, Yi Gang, Yongguo Zhang, Quanjiang Li, Taidong Qiao, Qingchuan Zhao, Yongzhan Nie, Daiming Fan
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2010-03-01
• Series: PLoS Genetics
• Online Access: http://europepmc.org/articles/PMC2837402?pdf=render
• ISSN: 1553-7390; 1553-7404

MicroRNAs play key roles in tumor metastasis. Here, we describe the regulation and function of miR-218 in gastric cancer (GC) metastasis. miR-218 expression is decreased along with the expression of one of its host genes, Slit3 in metastatic GC. However, Robo1, one of several Slit receptors, is negatively regulated by miR-218, thus establishing a negative feedback loop. Decreased miR-218 levels eliminate Robo1 repression, which activates the Slit-Robo1 pathway through the interaction between Robo1 and Slit2, thus triggering tumor metastasis. The restoration of miR-218 suppresses Robo1 expression and inhibits tumor cell invasion and metastasis in vitro and in vivo. Taken together, our results describe a Slit-miR-218-Robo1 regulatory circuit whose disruption may contribute to GC metastasis. Targeting miR-218 may provide a strategy for blocking tumor metastasis.