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


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.

SUBMITTER: Tie J 

PROVIDER: S-EPMC2837402 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature

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

Tie Jun J   Pan Yanglin Y   Zhao Lina L   Wu Kaichun K   Liu Jie J   Sun Shiren S   Guo Xuegang X   Wang Biaoluo B   Gang Yi Y   Zhang Yongguo Y   Li Quanjiang Q   Qiao Taidong T   Zhao Qingchuan Q   Nie Yongzhan Y   Fan Daiming D  

PLoS genetics 20100312 3


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 Rob  ...[more]

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