miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6.
- Author:
Fei LI
1
;
Xin ji LI
;
Li QIAO
;
Fei SHI
;
Wen LIU
;
You LI
;
Yu ping DANG
;
Wei jie GU
;
Xiao gang WANG
;
Wei LIU
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- MeSH: Animals; Cell Line, Tumor; Down-Regulation; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6/*genetics; Male; Melanoma/epidemiology/*genetics/*pathology; Mice; Mice, Inbred C57BL; MicroRNAs/*genetics; Neoplasm Metastasis/genetics/pathology; Signal Transduction; Survival Analysis
- From:Experimental & Molecular Medicine 2014;46(10):e116-
- CountryRepublic of Korea
- Language:English
- 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.
