Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Liu, SJ; Tetzlaff, MT; Liu, AH; Liegl-Atzwanger, B; Guo, J; Xu, XW; .
Loss of microRNA-205 expression is associated with melanoma progression.
Lab Invest. 2012; 92(7):1084-1096
Doi: 10.1038/labinvest.2012.62
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- Co-Autor*innen der Med Uni Graz
- Liegl-Atzwanger Bernadette
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- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Base Sequence -
- Cadherins - genetics Cadherins - metabolism
- Cell Line, Tumor -
- Cell Movement - genetics Cell Movement - physiology
- Cell Proliferation -
- DNA Primers - genetics
- Disease Progression -
- Epithelial-Mesenchymal Transition - genetics Epithelial-Mesenchymal Transition - physiology
- Homeodomain Proteins - genetics Homeodomain Proteins - metabolism
- Humans -
- Male -
- Melanoma - genetics Melanoma - metabolism Melanoma - pathology Melanoma - secondary
- Mice -
- Mice, Nude -
- MicroRNAs - genetics MicroRNAs - metabolism
- Nevus - genetics Nevus - metabolism Nevus - pathology
- Oligonucleotide Array Sequence Analysis -
- RNA, Neoplasm - genetics RNA, Neoplasm - metabolism
- Repressor Proteins - genetics Repressor Proteins - metabolism
- Skin Neoplasms - genetics Skin Neoplasms - metabolism Skin Neoplasms - pathology
- Transplantation, Heterologous -
- Find related publications in this database (Keywords)
- cell migration
- formalin-fixed paraffin embedded (FFPE)
- melanoma
- microarray
- miR-205
- miRNA