1.miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6.
Fei LI ; Xin ji LI ; Li QIAO ; Fei SHI ; Wen LIU ; You LI ; Yu ping DANG ; Wei jie GU ; Xiao gang WANG ; Wei LIU
Experimental & Molecular Medicine 2014;46(10):e116-
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-kappaB-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.
Animals
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Cell Line, Tumor
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Down-Regulation
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Gene Expression Regulation, Neoplastic
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Humans
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Interleukin-6/*genetics
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Male
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Melanoma/epidemiology/*genetics/*pathology
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Mice
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Mice, Inbred C57BL
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MicroRNAs/*genetics
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Neoplasm Metastasis/genetics/pathology
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Signal Transduction
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Survival Analysis