Exp Mol Med.
2014 Oct;46(10):e116. 10.1038/emm.2014.63.
miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6
- Affiliations
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- 1Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China. txg_wang@jnu.edu.cn lwei5811@126.com
- 2Department of Radiation Oncology, The Air Force General Hospital of PLA, Beijing, China.
- 3Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
- 4Jinan University and Hong Kong Baptist University Joint Laboratory of Innovative Drug Development, Jinan University, Guangzhou, China.
- KMID: 2155381
- DOI: http://doi.org/10.1038/emm.2014.63
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-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.
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