MTCH2 regulates NRF2-mediated RRM1 expression to promote melanoma proliferation and dacarbazine insensitivity

  • Cell Death Dis. 2025 Apr 9;16(1):268. doi: 10.1038/s41419-025-07618-9.
Xuedan Zhang  #  1 ,  Enjiang Li  #  1 ,  Yingmin Kuang  #  2 ,  Yanlong Gai  1 ,  Yu Feng  1 ,  Yu Huang  1 ,  Zhenyan Wei  1 ,  Junzi Niu  1 ,  Song Yu  1 ,  Zhe Yang  3 ,  Qiao Zhang  1 ,  Buqing Sai  4 ,  Yuechun Zhu  5
Affiliations
  • 1. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming, 650500, Yunnan, China.
  • 2. Department of Organ Transplantation, First Affiliated Hospital of Kunming Medical University, Kunming, 650500, Yunnan, China.
  • 3. Department of Pathology, First Affiliated Hospital of Kunming Medical University, Kunming, 650500, Yunnan, China.
  • 4. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming, 650500, Yunnan, China. [email protected].
  • 5. Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming, 650500, Yunnan, China. [email protected].
  • # Contributed equally.
PMID: 40204724 DOI: 10.1038/s41419-025-07618-9
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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