MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor.
MiR-218 inhibits invasion and metastasis of gastric cancer by targeting the Robo1 receptor.
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MiR-218通过靶向Robo1受体抑制胃癌的侵袭和转移。
DOI：
10.1371/journal.pgen.1000879
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发表时间：
2010-03-12
期刊：
影响因子：
4.5
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Tie J;Pan Y;Zhao L;Wu K;Liu J;Sun S;Guo X;Wang B;Gang Y;Zhang Y;Li Q;Qiao T;Zhao Q;Nie Y;Fan D
微小RNA（MicroRNAs）在肿瘤转移中起关键作用。在此，我们描述了miR - 218在胃癌（GC）转移中的调控及功能。在转移性胃癌中，miR - 218的表达与其宿主基因之一Slit3的表达一同降低。然而，Slit的几种受体之一Robo1受到miR - 218的负向调控，从而建立了一个负反馈回路。miR - 218水平降低消除了对Robo1的抑制，通过Robo1与Slit2之间的相互作用激活了Slit - Robo1通路，从而引发肿瘤转移。恢复miR - 218可抑制Robo1的表达，并在体外和体内抑制肿瘤细胞的侵袭和转移。综上所述，我们的研究结果描述了一个Slit - miR - 218 - Robo1调控回路，该回路的破坏可能导致胃癌转移。靶向miR - 218可能为阻断肿瘤转移提供一种策略。
微小RNA已被确定在肿瘤转移中起重要作用，但其对胃癌转移的影响尚未得到充分探究。我们发现了miR - 218，它作为肿瘤转移的抑制因子发挥作用，并且与胃癌患者的临床分期、淋巴结转移和预后相关。我们的研究结果表明，miR - 218是涉及Slit - Robo1通路的调控回路的一部分。在转移性肿瘤细胞中，miR - 218与它的宿主基因之一Slit3一同受到抑制。同时，Slit的几种受体之一Robo1因miR - 218的降低而上调，这反过来又通过与Slit2的相互作用诱导Slit - Robo1通路的反应性上调，从而促进肿瘤细胞的迁移和侵袭。这些发现不仅为胃癌转移机制提供了新的见解，还为一种新的微小RNA介导的受体信号调控模式提供了证据。
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. MicroRNAs have been identified as playing important roles in tumor metastasis, but their impact on GC metastasis has been poorly explored. We have discovered miR-218, which functions as a suppressor of tumor metastasis and is correlated with clinical stage, lymph node metastasis, and prognosis in patients with GC. Our results show that miR-218 is part of a regulatory circuit involving the Slit-Robo1 pathway. In metastatic tumor cells, miR-218 was suppressed along with Slit3, one of its host genes. Meanwhile, Robo1, one of several Slit receptors, is upregulated in response to the decrease in miR-218, which in turn induced a reactive upregulation of the Slit-Robo1 pathway through an interaction with Slit2, thus facilitating tumor cell migration and invasion. Such findings not only provide new insights into the metastatic mechanisms in GC but also provide evidence for a novel miRNA–mediated regulatory mode of receptor signaling.
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影响因子：
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作者：
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