Integration of zebrafish fin regeneration genes with expression data of human tumors in silico uncovers potential novel melanoma markers
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Martin Hagedorn1,2,3,*, Géraldine Siegfried1,2,*, Katarzyna B. Hooks1,3, Abdel-Majid Khatib1,2
1University of Bordeaux, Talence F-33405, France
2INSERM, LAMC, U1029, Talence F-33405, France
3INSERM, BMGIC, U1035, Bordeaux F-33000, France
*These authors contributed equally to this work
Martin Hagedorn, email: [email protected]
Abdel-Majid Khatib, email: [email protected]
Keywords: regeneration, melanoma, angiogenesis, BAMBI, FK506-binding proteins
Received: June 30, 2016 Accepted: September 19, 2016 Published: September 26, 2016
Tissue regeneration requires expression of a large, unknown number of genes to initiate and maintain cellular processes such as proliferation, extracellular matrix synthesis, differentiation and migration. A unique model to simulate this process in a controlled manner is the re-growth of the caudal fin of zebrafish after amputation. Within this tissue stem cells differentiate into fibroblasts, epithelial and endothelial cells as well as melanocytes. Many genes implicated in the regeneration process are deregulated in cancer. We therefore undertook a systematic gene expression study to identify genes upregulated during the re-growth of caudal fin tissue. By applying a high stringency cut-off value of 4-fold change, we identified 54 annotated genes significantly overexpressed in regenerating blastema. Further bioinformatics data mining studies showed that 22 out of the 54 regeneration genes where overexpressed in melanoma compared to normal skin or other cancers. Whereas the role of TNC (tenascin C) and FN1 (fibronectin 1) in melanoma development is well documented, implication of MARCKS, RCN3, BAMBI, PEA3/ETV4 and the FK506 family members FKBP7, FKBP10 and FKBP11 in melanoma progression is unclear. Corresponding proteins were detected in melanoma tissue but not in normal skin. High expression of FKBP7, DPYSL5 and MDK was significantly associated with poor survival. We discuss a potential role of these novel melanoma genes, which have promising potential as new therapeutic targets or diagnostic markers.
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