MiR-218 Inhibits Invasion and Metastasis of Gastric Cancer by Targeting the Robo1 Receptor |
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| 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 |
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| Institution: | State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi''an, Shaanxi, China;Fred Hutchinson Cancer Research Center, United States of America |
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| Abstract: | 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. |
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