2. Academic Validation
  3. HDAC3 and Snail2 complex promotes melanoma metastasis by epigenetic repression of IGFBP3

HDAC3 and Snail2 complex promotes melanoma metastasis by epigenetic repression of IGFBP3

  • Int J Biol Macromol. 2025 Apr:300:140310. doi: 10.1016/j.ijbiomac.2025.140310.
Nan Wu 1,  Qian Sun 2,  Liehao Yang 2,  Hongyan Sun 2,  Zilong Zhou 2,  Qianying Hu 2,  Chunyi Li 3,  Dongxu Wang 3,  Ling Zhang 4,  Yue Hu 5,  Xianling Cong 6
Affiliations

Affiliations

  • 1 Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun 130033, China; Phase I Clinical Trial Research Laboratory, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
  • 2 Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun 130033, China.
  • 3 Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun 130033, China.
  • 4 Key Laboratory of Pathobiology, Ministry of Education, and Department of Biomedical Science, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.
  • 5 Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun 130033, China. Electronic address: yuehu@jlu.edu.cn.
  • 6 Department of Biobank, China-Japan Union Hospital of Jilin University, Changchun 130033, China. Electronic address: congxl@jlu.edu.cn.
PMID: 39864688 DOI: 10.1016/j.ijbiomac.2025.140310
Abstract

The treatment of metastatic melanoma has long posed a complex challenge within clinical practice. Previous studies have found that EMT transcription factors are essential in the development of various cancers through their induction of EMT. Here, we demonstrate that Snail2 expression is dramatically increased in melanoma and is associated with an adverse prognosis. Elevated Snail2 in melanoma cells enhanced migratory and invasive capabilities in vitro and in vivo. Furthermore, RNA-Seq analysis revealed a significant reduction of IGFBP3 expression in melanoma cells overexpressing Snail2. IGFBP3 might mitigate the Snail2's ability to promote melanoma metastasis via the PI3K-AKT pathway. Moreover, Snail2 and HDAC3 collaborate to suppress IGFBP3 transcription through H3K4 deacetylation and H4K5 delactylation. Additionally, the combination of HDAC3 and p-GSK-3β inhibitors significantly improved the treatment outcomes for lung metastasis in melanoma in vivo. The results of our study indicate that Snail2, HDAC3, and IGFBP3 play significant roles in melanoma progression and represent promising therapeutic targets.

Keywords

EMT; Melanoma; Metastasis; Snail2.

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