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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.
Subject(s)
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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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