PUBLICATION

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

Authors
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.
ID
ZDB-PUB-181127-45
Date
2018
Source
Cells   7(11): (Journal)
Registered Authors
Tiso, Natascia
Keywords
CRISPR/Cas9, RUNT, RUNX2, melanoma
MeSH Terms
none
PubMed
30463392 Full text @ Cells
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.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes