MITF regulates IDH1, NNT, and a transcriptional program protecting melanoma from reactive oxygen species
Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte function, development and plays a significant role in melanoma pathogenesis. MITF genomic amplification promotes melanoma development, and it can facilitate resistance to multiple therapies. Here, we show that...
Elmentve itt :
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| Dokumentumtípus: | Cikk |
| Megjelent: |
2024
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| Sorozat: | SCIENTIFIC REPORTS
14 No. 1 |
| Tárgyszavak: | |
| doi: | 10.1038/s41598-024-72031-9 |
| mtmt: | 35295966 |
| Online Access: | http://publicatio.bibl.u-szeged.hu/35051 |
| Tartalmi kivonat: | Microphthalmia-associated transcription factor (MITF) is a master regulator of melanocyte function, development and plays a significant role in melanoma pathogenesis. MITF genomic amplification promotes melanoma development, and it can facilitate resistance to multiple therapies. Here, we show that MITF regulates a global antioxidant program that increases survival of melanoma cell lines by protecting the cells from reactive oxygen species (ROS)-induced damage. In addition, this redox program is correlated with MITF expression in human melanoma cell lines and patient-derived melanoma samples. Using a zebrafish melanoma model, we show that MITF decreases ROS-mediated DNA damage in vivo. Some of the MITF target genes involved, such as IDH1 and NNT , are regulated through direct MITF binding to canonical enhancer box (E-BOX) sequences proximal to their promoters. Utilizing functional experiments, we demonstrate the role of MITF and its target genes in reducing cytosolic and mitochondrial ROS. Collectively, our data identify MITF as a significant driver of the cellular antioxidant state. |
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| Terjedelem/Fizikai jellemzők: | 13 |
| ISSN: | 2045-2322 |