PUBLICATION

MITF regulates IDH1, NNT, and a transcriptional program protecting melanoma from reactive oxygen species

Authors
Roider, E., Lakatos, A.I.T., McConnell, A.M., Wang, P., Mueller, A., Kawakami, A., Tsoi, J., Szabolcs, B.L., Ascsillán, A.A., Suita, Y., Igras, V., Lo, J.A., Hsiao, J.J., Lapides, R., Pál, D.M.P., Lengyel, A.S., Navarini, A., Okazaki, A., Iliopoulos, O., Németh, I., Graeber, T.G., Zon, L., Giese, R.W., Kemeny, L.V., Fisher, D.E.
ID
ZDB-PUB-240916-9
Date
2024
Source
Scientific Reports   14: 2152721527 (Journal)
Registered Authors
Zon, Leonard I.
Keywords
none
MeSH Terms
  • Cell Line, Tumor
  • Melanoma*/genetics
  • Melanoma*/metabolism
  • Melanoma*/pathology
  • Isocitrate Dehydrogenase*/genetics
  • Isocitrate Dehydrogenase*/metabolism
  • Zebrafish*
  • Animals
  • DNA Damage
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Transcription, Genetic
  • Reactive Oxygen Species*/metabolism
  • Microphthalmia-Associated Transcription Factor*/genetics
  • Microphthalmia-Associated Transcription Factor*/metabolism
(all 17)
PubMed
39277608 Full text @ Sci. Rep.
Abstract
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.
Genes / Markers
Figures
Figure Gallery (4 images)
Show all Figures
Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
czt13TgTransgenic Insertion
    w2
      		Point Mutation
      zdf1
        		Point Mutation
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        No data available
        Fish
        No data available
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        No data available
        Mapping
        No data available
        Your Input Welcome
        We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
        Citation
        Roider, E., Lakatos, A.I.T., McConnell, A.M., Wang, P., Mueller, A., Kawakami, A., Tsoi, J., Szabolcs, B.L., Ascsillán, A.A., Suita, Y., Igras, V., Lo, J.A., Hsiao, J.J., Lapides, R., Pál, D.M.P., Lengyel, A.S., Navarini, A., Okazaki, A., Iliopoulos, O., Németh, I., Graeber, T.G., Zon, L., Giese, R.W., Kemeny, L.V., Fisher, D.E. (2024) MITF regulates IDH1, NNT, and a transcriptional program protecting melanoma from reactive oxygen species. Scientific Reports. 14:2152721527.