RESUMO
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.
Assuntos
Animais , Humanos , Masculino , Camundongos , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Interleucina-6/genética , Melanoma/epidemiologia , Camundongos Endogâmicos C57BL , MicroRNAs/genética , Metástase Neoplásica/genética , Transdução de Sinais , Análise de SobrevidaRESUMO
OBJECTIVES: To study the effect of antisperm antibody(AsAb) on human sperm acrosin activity. METHODS: AsAb and sperm acrosin activity were measured and analyzed in 3,432 infertile men and 65 fertile volunteers. RESULTS: AsAb positive rate was 10.20% in 3,432 case of male infertility, and 9.37% in 2,882 infertile males who received tests of sperm acrosin activity. Acrosin activity of infertility cases were lower than those of fertile cases(P < 0.001). The comparison between AsAb positive group and AsAb negative group infertility cases showed no significant differences of acrosin activity (P > 0.05). Between normal acrosin activity group and abnormal acrosin activity group, there was no significant difference of AsAb positive rate (P > 0.05). CONCLUSIONS: Antisperm antibody could not affect acrosin activity.