miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6.

miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6. Exp Mol Med. 2014;46:e116 Authors: Li F, Li XJ, Qiao L, Shi F, Liu W, Li Y, Dang YP, Gu WJ, Wang XG, Liu W 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. PMID: 25277211 [PubMed - in process]
Source: exp Mol Med - Category: Molecular Biology Authors: Tags: Exp Mol Med Source Type: research