title: Loss of microRNA-205 expression is associated with melanoma progression.
abstract: In this study, we used formalin-fixed paraffin-embedded melanocytic tumors to demonstrate reproducible alterations in microRNA expression in nevi compared with melanomas using a microarray platform. We validated those results in an independent set of nevi and melanomas by quantitative RT-PCR. miR-205 demonstrated a statistically significant, progressive diminution in expression from nevi to primary melanomas to metastatic melanomas. Enforced miR-205 expression in melanoma cells profoundly impairs cell motility and migration along with significantly decreased F-actin polymerization with only a modest reduction in cell proliferation. Using a xenograft model, melanoma cells overexpressing miR-205 exhibit a reduced migratory capacity compared with control tumor cells. Mechanistically, miR-205 overexpression results in decreased expression of the zinc-finger E-box binding homeobox 2 (ZEB2) mRNA and protein. This coincides with increased expression of E-cadherin mRNA and protein. Furthermore, re-introduction of ZEB2 into melanoma cells overexpressing miR-205 rescues these phenotypic effects and results in a restoration of cell migration and F-actin polymerization with a concomitant reduction in E-cadherin expression. Together, these results provide in vitro and in vivo evidence for miR-205 as a critical suppressor of melanoma cell migration.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Hospital of the University of Pennsylvania, Philadelphia, USA.
authors.forename: Shujing
authors.initials: S
authors.lastname: Liu
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.forename: Aihua
authors.initials: A
authors.lastname: Liu
authors.forename: Bernadette
authors.initials: B
authors.lastname: Liegl-Atzwanger
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D017931:DNA Primers / Q000235:genetics; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D009506:Nevus / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D014183:Transplantation, Heterologous; D000074165:Zinc Finger E-box Binding Homeobox 2
chemical_list: D015820:Cadherins; D017931:DNA Primers; D018398:Homeodomain Proteins; D035683:MicroRNAs; D012334:RNA, Neoplasm; D012097:Repressor Proteins; D000074165:Zinc Finger E-box Binding Homeobox 2; C534425:MIR205, human; C492363:ZEB2 protein, human