An m5C-associated NSUN5–YBX1–CENPF programme marks melanoma cell states and immune features
4 affiliations
- 1Skin Structure and Function Key Laboratory of Luzhou, Department of Dermatology, The Affiliated Hospital of Southwest Medical University
- 2Department of Dermatology, The Second Affiliated Hospital of Chengdu Medical College, China National Nuclear Corporation 416 Hospital
- 3Clinical Medical College, Southwest Medical University
- 4Department of Dermatology, Chengdu Integrated TCM & Western Medicine Hospital, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine
Abstract
Background: RNA 5-methylcytosine (m ⁵ C)-associated programmes may help characterise melanoma cell states and their immune context. We investigated an NSUN5–YBX1–CENPF (NYC) programme using patient-matched sequencing, experimental perturbation and multiscale transcriptomic analyses.
Methods: We analysed m ⁵ C-MeRIP-seq and matched Input RNA data from three melanoma–adjacent-normal patient pairs, using a paired edgeR interaction model for regional IP enrichment. Tissue and cell experiments included NSUN5 knockdown, CENPF-targeted MeRIP–qPCR and western blotting. Clinical analyses considered proliferation and sampling site. Trajectory and regulatory inference were restricted to malignant cells from GSE215120, with patient-level summaries. Treatment-associated changes were examined in 43 paired patients from GSE91061. Computational perturbation and transcriptomic signature reversal prioritised candidate regulators and compounds.
Results: Two CENPF regions showed increased relative IP enrichment after Input adjustment (4.97- and 5.85-fold; BH q = 0.0457 and 0.0074). NSUN5 knockdown reduced CENPF m ⁵ C enrichment and protein abundance. NYC was associated with proliferation; its survival association did not persist after proliferation adjustment. Within malignant cells, NYC-High retained an association with an immune-resistance expression programme after G2M/E2F and depth adjustment (nine patients; BH q = 0.0156). Regulatory analyses prioritised MLX, whose simulated knockout and overexpression produced opposing reference-flow alignments (BH q = 0.0134 and 0.0201). MLX regulon activity was associated with glycolysis and oxidative phosphorylation after adjustment. In GSE91061, responders showed a greater treatment-associated NYC decrease than non-responders (mean change difference −0.209; permutation P = 0.0138). Drug screening generated candidates for experimental testing.
Conclusions: NYC provides an m ⁵ C-associated framework connecting patient-derived molecular observations to malignant-cell states and immune features. YBX1 remains a candidate reader, and regulatory, treatment-associated and drug-prioritisation findings do not establish a complete causal pathway or a clinically validated predictive biomarker.
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BibTeX
@article{liu2026m5cassociated,
title = {{An m5C-associated NSUN5–YBX1–CENPF programme marks melanoma cell states and immune features}},
author = {Aimei Liu and Kun Yuan and Sha Yi and Hanxiao Mao and Xinyu Xie and Shiyang Yin and Haonan Fan and Ailin Zhang and Xixu Liu and Yifu Hu and Aiguo Xu and Wei Chen and Yuanmin He},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1952519},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952519/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - An m5C-associated NSUN5–YBX1–CENPF programme marks melanoma cell states and immune features
AU - Aimei Liu
AU - Kun Yuan
AU - Sha Yi
AU - Hanxiao Mao
AU - Xinyu Xie
AU - Shiyang Yin
AU - Haonan Fan
AU - Ailin Zhang
AU - Xixu Liu
AU - Yifu Hu
AU - Aiguo Xu
AU - Wei Chen
AU - Yuanmin He
PY - 2026
DA - 2026/10/16
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1952519
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1952519/full
AB - Background: RNA 5-methylcytosine (m ⁵ C)-associated programmes may help characterise melanoma cell states and their immune context. We investigated an NSUN5–YBX1–CENPF (NYC) programme using patient-matched sequencing, experimental perturbation and multiscale transcriptomic analyses. Methods: We analysed m ⁵ C-MeRIP-seq and matched Input RNA data from three melanoma–adjacent-normal patient pairs, using a paired edgeR interaction model for regional IP enrichment. Tissue and cell experiments included NSUN5 knockdown, CENPF-targeted MeRIP–qPCR and western blotting. Clinical analyses considered proliferation and sampling site. Trajectory and regulatory inference were restricted to malignant cells from GSE215120, with patient-level summaries. Treatment-associated changes were examined in 43 paired patients from GSE91061. Computational perturbation and transcriptomic signature reversal prioritised candidate regulators and compounds. Results: Two CENPF regions showed increased relative IP enrichment after Input adjustment (4.97- and 5.85-fold; BH q = 0.0457 and 0.0074). NSUN5 knockdown reduced CENPF m ⁵ C enrichment and protein abundance. NYC was associated with proliferation; its survival association did not persist after proliferation adjustment. Within malignant cells, NYC-High retained an association with an immune-resistance expression programme after G2M/E2F and depth adjustment (nine patients; BH q = 0.0156). Regulatory analyses prioritised MLX, whose simulated knockout and overexpression produced opposing reference-flow alignments (BH q = 0.0134 and 0.0201). MLX regulon activity was associated with glycolysis and oxidative phosphorylation after adjustment. In GSE91061, responders showed a greater treatment-associated NYC decrease than non-responders (mean change difference −0.209; permutation P = 0.0138). Drug screening generated candidates for experimental testing. Conclusions: NYC provides an m ⁵ C-associated framework connecting patient-derived molecular observations to malignant-cell states and immune features. YBX1 remains a candidate reader, and regulatory, treatment-associated and drug-prioritisation findings do not establish a complete causal pathway or a clinically validated predictive biomarker.
SN - 1664-3224
ER -