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KMID : 0620920140460100002
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Experimental & Molecular Medicine
2014 Volume.46 No. 10 p.2 ~ p.2
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miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6
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Fei Li
Xin-ji Li
Li Qiao
Fei Shi
Wen Liu
You Li
Yu-ping Dang
Wei-jie Gu
Xiao-gang Wang
Wei Liu
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Abstract
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Dysregulated microRNA (miRNA) expression has a critical role in tumor development and metastasis. However, the mechanism by which miRNAs control melanoma metastasis is unknown. Here, we report reduced miR-98 expression in melanoma tissues with increasing tumor stage as well as metastasis; its expression is also negatively associated with melanoma patient survival. Furthermore, we demonstrate that miR-98 inhibits melanoma cell migration in vitro as well as metastatic tumor size in vivo. We also found that IL-6 is a target gene of miR-98, and IL-6 represses miR-98 levels via the Stat3-NF-κB-lin28B pathway. In an in vivo melanoma model, we demonstrate that miR-98 reduces melanoma metastasis and increases survival in part by reducing IL-6 levels; it also decreases Stat3 and p65 phosphorylation as well as lin28B mRNA levels. These results suggest that miR-98 inhibits melanoma metastasis in part through a novel miR-98-IL-6-negative feedback loop.
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