title: miR-98 suppresses melanoma metastasis through a negative feedback loop with its target gene IL-6.
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.
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Xin-ji
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Shi
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: You
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Yu-ping
authors.initials: YP
authors.lastname: Dang
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Wei-jie
authors.initials: WJ
authors.lastname: Gu
authors.affiliation: 1] Department of Cell Biology and Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, China [2] Jinan University and Hong Kong Baptist University Joint Laboratory of Innovative Drug Development, Jinan University, Guangzhou, China.
authors.forename: Xiao-gang
authors.initials: XG
authors.lastname: Wang
authors.affiliation: Department of Dermatology, The Air Force General Hospital of PLA, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology; D015398:Signal Transduction; D016019:Survival Analysis
chemical_list: D015850:Interleukin-6; C546084:MIRN98 microRNA, human; C557404:MIRN98 microRNA, mouse; D035683:MicroRNAs