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Cells 2018, 7(11), 220; https://doi.org/10.3390/cells7110220

New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration

1
Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, Italy
2
Department of Medicine, University of Verona, I-37134 Verona, Italy
3
Department of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, I-37134 Verona, Italy
4
Department of Sciences and Technological Innovation, University of Piemonte Orientale, I-15121 Alessandria, Italy
5
Proteomics and Mass Spectrometry Laboratory, Department of Biotechnology, University of Verona, I-37134 Verona, Italy
6
Department of Biology, University of Padova, I-35131 Padova, Italy
*
Author to whom correspondence should be addressed.
Received: 5 October 2018 / Revised: 15 November 2018 / Accepted: 16 November 2018 / Published: 20 November 2018
(This article belongs to the Section Cell Motility and Adhesion)
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Abstract

The mortality rate for malignant melanoma (MM) is very high, since it is highly invasive and resistant to chemotherapeutic treatments. The modulation of some transcription factors affects cellular processes in MM. In particular, a higher expression of the osteogenic master gene RUNX2 has been reported in melanoma cells, compared to normal melanocytes. By analyzing public databases for recurrent RUNX2 genetic and epigenetic modifications in melanoma, we found that the most common RUNX2 genetic alteration that exists in transcription upregulation is, followed by genomic amplification, nucleotide substitution and multiple changes. Additionally, altered RUNX2 is involved in unchecked pathways promoting tumor progression, Epithelial Mesenchymal Transition (EMT), and metastasis. In order to investigate further the role of RUNX2 in melanoma development and to identify a therapeutic target, we applied the CRISPR/Cas9 technique to explore the role of the RUNT domain of RUNX2 in a melanoma cell line. RUNT-deleted cells showed reduced proliferation, increased apoptosis, and reduced EMT features, suggesting the involvement of the RUNT domain in different pathways. In addition, del-RUNT cells showed a downregulation of genes involved in migration ability. In an in vivo zebrafish model, we observed that wild-type melanoma cells migrated in 81% of transplanted fishes, while del-RUNT cells migrated in 58%. All these findings strongly suggest the involvement of the RUNT domain in melanoma metastasis and cell migration and indicate RUNX2 as a prospective target in MM therapy. View Full-Text
Keywords: RUNT; RUNX2; CRISPR/Cas9; melanoma RUNT; RUNX2; CRISPR/Cas9; melanoma
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Deiana, M.; Dalle Carbonare, L.; Serena, M.; Cheri, S.; Parolini, F.; Gandini, A.; Marchetto, G.; Innamorati, G.; Manfredi, M.; Marengo, E.; Brandi, J.; Cecconi, D.; Mori, A.; Mina, M.M.; Antoniazzi, F.; Mottes, M.; Tiso, N.; Malerba, G.; Zipeto, D.; Valenti, M.T. New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration. Cells 2018, 7, 220.

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