ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicMelanoma Therapeutics at the CrossroadsView all 4 articles
Histone-related gene WDR77 promotes tumor progression through cell cycle regulation in skin cutaneous melanoma
Provisionally accepted
- Anhui Medical University, Hefei, China
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Skin cutaneous melanoma (SKCM) is extremely malignant, leading to poor prognosis. Epigenetic dysregulation, particularly histone modifications, contributes to disease progression. However, effective histone-based prognostic biomarkers are still lacking for the clinic. Here, we applied integrative machine learning approaches to generate a robust histone-related prognostic signature. WDR77, a histone methylation factor co-working with PRMT5 was identified as a key candidate. In SKCM, WDR77 was significantly upregulated. Patients with high WDR77 levels also have worse outcomes, making it a strong prognostic marker. Pathway enrichment analyses discovered that WDR77 primarily associates with cell-cycle dysregulation. CDC20, a cell cycle factor, emerged as a key co-expressed gene. Patients with concurrent high expression of WDR77 and CDC20 had the worst survival outcomes. Single-cell analyses confirmed its predominant expression in malignant cells across pan-cancer datasets and significant positive correlations with CDC20. Spatial transcriptomics validated their co-localization and concurrent elevation within tumor regions. Functional experiments showed that WDR77 promotes proliferation, migration, and cell cycle progression, and its overexpression increases CDC20 protein levels. This study identifies WDR77 as both a prognostic biomarker and functional regulator in melanoma, highlighting its potential as a therapeutic target.
Keywords: Melanoma, histone, WDR77, Cell Cycle, cdc20, Prognosis biomarker, Therapeutic target
Received: 13 Apr 2025; Accepted: 19 Nov 2025.
Copyright: © 2025 Zhang, Tang, Liu and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Shengxiu Liu, liushengxiu@ahmu.edu.cn
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