MTCH2 regulates NRF2-mediated RRM1 expression to promote melanoma proliferation and dacarbazine insensitivity
Abstract Melanoma is among the 10 most prevalent malignant tumors, posing a significant threat to human health. A detailed understanding of the molecular mechanisms driving its progression is crucial for advancing treatment strategies and outcomes. Based on bioinformatic analysis and experimental va...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-04-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07618-9 |
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| Summary: | Abstract Melanoma is among the 10 most prevalent malignant tumors, posing a significant threat to human health. A detailed understanding of the molecular mechanisms driving its progression is crucial for advancing treatment strategies and outcomes. Based on bioinformatic analysis and experimental validation, this study identified mitochondrial carrier homolog 2 (MTCH2) as a key regulator of melanoma proliferation. Mechanistically, MTCH2 enhanced the expression and nuclear translocation of nuclear factor (erythroid-derived-2)-like 2 (NRF2), which up-regulated ribonucleotide reductase subunit M1 (RRM1) expression, thereby promoting melanoma cell proliferation. Targeting RRM1 in combination with dacarbazine significantly inhibited tumor growth in nude mouse xenograft models. These findings elucidate a mechanistic link between MTCH2 and the NRF2-RRM1 axis in melanoma proliferation and highlight potential therapeutic targets for intervention. |
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| ISSN: | 2041-4889 |