miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6 |
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| Authors: | 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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| Institution: | 1.Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China;2.Department of Radiation Oncology, The Air Force General Hospital of PLA, Beijing, China;3.Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China;4.Jinan University and Hong Kong Baptist University Joint Laboratory of Innovative Drug Development, Jinan University, Guangzhou, China |
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| Abstract: | 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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