PLoS Genetics (Mar 2010)

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

  • 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

DOI
https://doi.org/10.1371/journal.pgen.1000879
Journal volume & issue
Vol. 6, no. 3
p. e1000879

Abstract

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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.