New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration
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 report...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-11-01
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| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/7/11/220 |
| id |
doaj-6f997a9227dd4a0f8e560eb4e31775c4 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Michela Deiana Luca Dalle Carbonare Michela Serena Samuele Cheri Francesca Parolini Alberto Gandini Giulia Marchetto Giulio Innamorati Marcello Manfredi Emilio Marengo Jessica Brandi Daniela Cecconi Antonio Mori Maria Mihaela Mina Franco Antoniazzi Monica Mottes Natascia Tiso Giovanni Malerba Donato Zipeto Maria Teresa Valenti |
| spellingShingle |
Michela Deiana Luca Dalle Carbonare Michela Serena Samuele Cheri Francesca Parolini Alberto Gandini Giulia Marchetto Giulio Innamorati Marcello Manfredi Emilio Marengo Jessica Brandi Daniela Cecconi Antonio Mori Maria Mihaela Mina Franco Antoniazzi Monica Mottes Natascia Tiso Giovanni Malerba Donato Zipeto Maria Teresa Valenti New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration Cells RUNT RUNX2 CRISPR/Cas9 melanoma |
| author_facet |
Michela Deiana Luca Dalle Carbonare Michela Serena Samuele Cheri Francesca Parolini Alberto Gandini Giulia Marchetto Giulio Innamorati Marcello Manfredi Emilio Marengo Jessica Brandi Daniela Cecconi Antonio Mori Maria Mihaela Mina Franco Antoniazzi Monica Mottes Natascia Tiso Giovanni Malerba Donato Zipeto Maria Teresa Valenti |
| author_sort |
Michela Deiana |
| title |
New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration |
| title_short |
New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration |
| title_full |
New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration |
| title_fullStr |
New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration |
| title_full_unstemmed |
New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and Migration |
| title_sort |
new insights into the runt domain of runx2 in melanoma cell proliferation and migration |
| publisher |
MDPI AG |
| series |
Cells |
| issn |
2073-4409 |
| publishDate |
2018-11-01 |
| description |
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. |
| topic |
RUNT RUNX2 CRISPR/Cas9 melanoma |
| url |
https://www.mdpi.com/2073-4409/7/11/220 |
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1725634279223853056 |
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doaj-6f997a9227dd4a0f8e560eb4e31775c42020-11-24T23:03:21ZengMDPI AGCells2073-44092018-11-0171122010.3390/cells7110220cells7110220New Insights into the Runt Domain of RUNX2 in Melanoma Cell Proliferation and MigrationMichela Deiana0Luca Dalle Carbonare1Michela Serena2Samuele Cheri3Francesca Parolini4Alberto Gandini5Giulia Marchetto6Giulio Innamorati7Marcello Manfredi8Emilio Marengo9Jessica Brandi10Daniela Cecconi11Antonio Mori12Maria Mihaela Mina13Franco Antoniazzi14Monica Mottes15Natascia Tiso16Giovanni Malerba17Donato Zipeto18Maria Teresa Valenti19Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Medicine, University of Verona, I-37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, I-37134 Verona, ItalyDepartment of Medicine, University of Verona, I-37134 Verona, ItalyDepartment of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, I-37134 Verona, ItalyDepartment of Sciences and Technological Innovation, University of Piemonte Orientale, I-15121 Alessandria, ItalyDepartment of Sciences and Technological Innovation, University of Piemonte Orientale, I-15121 Alessandria, ItalyProteomics and Mass Spectrometry Laboratory, Department of Biotechnology, University of Verona, I-37134 Verona, ItalyProteomics and Mass Spectrometry Laboratory, Department of Biotechnology, University of Verona, I-37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Medicine, University of Verona, I-37134 Verona, ItalyDepartment of Surgery, Dentistry, Pediatrics and Gynecology, University of Verona, I-37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Biology, University of Padova, I-35131 Padova, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, I-37134 Verona, ItalyDepartment of Medicine, University of Verona, I-37134 Verona, ItalyThe 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.https://www.mdpi.com/2073-4409/7/11/220RUNTRUNX2CRISPR/Cas9melanoma |