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From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review)

  • Authors:
    • Jingwen Wu
    • Xuxia Cai
    • Zimo Zhu
    • Xiahong Li
    • Kaoyuan Zhang
    • Chenchen Wu
    • Bo Yu
    • Cong Huang
  • View Affiliations / Copyright

    Affiliations: Department of Dermatology, Skin Research Institute of Peking University Shenzhen Hospital, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 15
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    Published online on: November 12, 2025
       https://doi.org/10.3892/or.2025.9020
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Abstract

Melanoma, a highly malignant form of skin cancer, poses significant challenges in oncology due to its aggressive nature and resistance to conventional therapies. Epigenetic modifications, especially acetylation, have emerged as critical regulators of gene expression that influence the pathogenesis and progression of melanoma. Acetylation is a novel post‑translational modification that involves the addition of an acetyl group to lysine residues both in histone and in non‑histone proteins. In the context of melanoma, acetylation has been shown to occupy a pivotal role in regulating cellular proliferation, autophagy, apoptosis and metastasis, as well as drug resistance. The identification of acetylation‑associated biomarkers and therapeutic targets in melanoma is currently an active area of research. The present review aims to elucidate the roles of acetylation modifications in melanoma, and to explore the potential of targeting these modifications for novel therapeutic interventions, with a unique perspective on the acetylation networks mediating therapy resistance.
View Figures

Figure 1

Acetylation-mediated regulation of
melanoma progression. P300 enhances melanoma cell proliferation via
acetylation of cyclin E, MITF, BRAF and c-Myc. EZH2 represses p21
through HDAC1, disrupting the cell cycle. HDAC6 modulates
proliferation, autophagy, and apoptosis via α-tubulin, HSP90,
cortactin, and the PTPN1-ERK1/2 pathway; its inhibition induces
apoptosis via Bcl-2/Bax regulation. HDAC7 promotes growth via
c-Myc, while P300 and HDAC10 coordinate SPARC-mediated autophagy.
SIRT1 and SIRT6 regulate apoptosis and autophagy through CHK2 and
IGF-AKT signaling, respectively. HDAC1/2 activate BMP6-SMAD5 to
inhibit metastasis, while HDAC8 enhances invasion via deacetylation
of HIF-1α and EP300. SIRT1 promotes migration through EMT,
lamellipodia formation, and AKT deacetylation; SIRT6 antagonizes
this effect. SIRT2 and SIRT6 drive resistance via MEK-ERK and
IGF-AKT signaling. SIRT7 promotes PD-L1-mediated immune evasion by
suppressing TGF-β-SMAD4 signaling. HDAC, histone deacetylase; EMT,
epithelial-mesenchymal transition.

Figure 2

Integrated signaling pathways and
targeted therapeutic agents in melanoma. Pathways are outlined in
red boxes with directional arrows. Drug categories are color-coded
in light green. Schematic depicts interconnected pathways driving
melanoma pathogenesis: CBP/P300 and HDAC 7/8/6 regulate the
expression of c-Myc, MEK and ERK. SIRT6 is the downstream product
of the PI3K-AKT pathway and P300-MITF-FOXM1 transcriptional network
controlling melanocyte differentiation and proliferation.
HDAC1/2-BMP6-SMAD5 pathway modulating TGF-β signaling.
HDAC6-selective inhibitors (HDAC6i): ACY-1215, ACY-241, Suprastat,
MGCD0103, MS275, and romidepsin. Pan-HDAC inhibitors (Pan-HDACi):
AR42/sodium valproate, quisinostat, panobinostat, LAQ824, and
LBH589. Acetylation-targeting agents: Rg3, C646, HINT1,
isothiocyanates, metformin, and TH9. HDAC, histone deacetylase;
HDACi, HDAC inhibitor.
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Copy and paste a formatted citation
Spandidos Publications style
Wu J, Cai X, Zhu Z, Li X, Zhang K, Wu C, Yu B and Huang C: From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review). Oncol Rep 55: 15, 2026.
APA
Wu, J., Cai, X., Zhu, Z., Li, X., Zhang, K., Wu, C. ... Huang, C. (2026). From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review). Oncology Reports, 55, 15. https://doi.org/10.3892/or.2025.9020
MLA
Wu, J., Cai, X., Zhu, Z., Li, X., Zhang, K., Wu, C., Yu, B., Huang, C."From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review)". Oncology Reports 55.1 (2026): 15.
Chicago
Wu, J., Cai, X., Zhu, Z., Li, X., Zhang, K., Wu, C., Yu, B., Huang, C."From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review)". Oncology Reports 55, no. 1 (2026): 15. https://doi.org/10.3892/or.2025.9020
Copy and paste a formatted citation
x
Spandidos Publications style
Wu J, Cai X, Zhu Z, Li X, Zhang K, Wu C, Yu B and Huang C: From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review). Oncol Rep 55: 15, 2026.
APA
Wu, J., Cai, X., Zhu, Z., Li, X., Zhang, K., Wu, C. ... Huang, C. (2026). From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review). Oncology Reports, 55, 15. https://doi.org/10.3892/or.2025.9020
MLA
Wu, J., Cai, X., Zhu, Z., Li, X., Zhang, K., Wu, C., Yu, B., Huang, C."From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review)". Oncology Reports 55.1 (2026): 15.
Chicago
Wu, J., Cai, X., Zhu, Z., Li, X., Zhang, K., Wu, C., Yu, B., Huang, C."From modification to malignancy: Bridging acetylation mechanisms and therapeutic innovations in melanoma (Review)". Oncology Reports 55, no. 1 (2026): 15. https://doi.org/10.3892/or.2025.9020
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