miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6
Experimental & Molecular Medicine
;
: e116-2014.
Article
in English
| WPRIM
| ID: wpr-222036
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Signal Transduction
/
Down-Regulation
/
Gene Expression Regulation, Neoplastic
/
Survival Analysis
/
Interleukin-6
/
MicroRNAs
/
Cell Line, Tumor
/
Melanoma
/
Mice, Inbred C57BL
/
Neoplasm Metastasis
Type of study:
Prognostic study
Limits:
Animals
/
Humans
/
Male
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2014
Type:
Article
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