Multi-Omic Analyses Reveal VPS72 Associations with Chromatin Remodeling, Proliferation, and Stress-Response Programs Across Human Cancers
4 affiliations
- 1Center for Cutaneous Biology and Immunology Research, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA
- 2Immunology Research Program, Henry Ford Cancer Institute, Henry Ford Health, Detroit, MI 48202, USA
- 3Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA
- 4Department of Public Health, Henry Ford Health, Detroit, MI 48202, USA
Abstract
Malignant cells hijack epigenetic processes to sustain proliferation and to tolerate stressors that would otherwise limit cell growth, yet the chromatin remodeling activities that establish and maintain these programs are poorly defined. H2A.Z is a histone variant deposited into nucleosomes by the SRCAP and TIP60 chromatin-remodeling complexes, which share VPS72 as a chaperone subunit. VPS72 is located at 1q21, a region recurrently gained in human cancers, yet its contribution to tumor biology remains largely unexplored. Here, we show that VPS72 copy-number gain occurs in more than one-third of tumors and its expression is enriched beyond that expected from neighboring 1q21 genes and remains elevated over normal tissue in copy-neutral tumors. Across cancer types, higher VPS72 expression was associated with proliferative transcriptional programs, cell-cycle–related chromatin accessibility, and genomic instability. Single-cell analyses localized these associations primarily to malignant cells. Higher VPS72 expression and copy-number gain were associated with shorter overall survival in several solid tumors, although these relationships varied by lineage. VPS72 copy-number gain was also associated with shorter overall survival after adjustment for age and sex. Cancer-cell screens further identified recurrent VPS72 dependency, and VPS72 depletion suppressed proliferative programs while inducing stress, inflammatory, and apoptotic responses that were only partly shared with H2A.Z depletion. Together, these findings identify VPS72 as a recurrently altered component of tumor chromatin regulation associated with proliferative and stress-response states and support further investigation of its therapeutic significance.
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BibTeX
@article{solone2026multiomic,
title = {{Multi-Omic Analyses Reveal VPS72 Associations with Chromatin Remodeling, Proliferation, and Stress-Response Programs Across Human Cancers}},
author = {Xzaviar K. Solone and Md-Selim Reza and Paul Renauer and Kalpana Subedi and Nirmal Parajuli and Li Zhou and Qing-Sheng Mi},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27209367},
url = {https://www.mdpi.com/1422-0067/27/20/9367},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multi-Omic Analyses Reveal VPS72 Associations with Chromatin Remodeling, Proliferation, and Stress-Response Programs Across Human Cancers
AU - Xzaviar K. Solone
AU - Md-Selim Reza
AU - Paul Renauer
AU - Kalpana Subedi
AU - Nirmal Parajuli
AU - Li Zhou
AU - Qing-Sheng Mi
PY - 2026
DA - 2026/10/21
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27209367
UR - https://www.mdpi.com/1422-0067/27/20/9367
AB - Malignant cells hijack epigenetic processes to sustain proliferation and to tolerate stressors that would otherwise limit cell growth, yet the chromatin remodeling activities that establish and maintain these programs are poorly defined. H2A.Z is a histone variant deposited into nucleosomes by the SRCAP and TIP60 chromatin-remodeling complexes, which share VPS72 as a chaperone subunit. VPS72 is located at 1q21, a region recurrently gained in human cancers, yet its contribution to tumor biology remains largely unexplored. Here, we show that VPS72 copy-number gain occurs in more than one-third of tumors and its expression is enriched beyond that expected from neighboring 1q21 genes and remains elevated over normal tissue in copy-neutral tumors. Across cancer types, higher VPS72 expression was associated with proliferative transcriptional programs, cell-cycle–related chromatin accessibility, and genomic instability. Single-cell analyses localized these associations primarily to malignant cells. Higher VPS72 expression and copy-number gain were associated with shorter overall survival in several solid tumors, although these relationships varied by lineage. VPS72 copy-number gain was also associated with shorter overall survival after adjustment for age and sex. Cancer-cell screens further identified recurrent VPS72 dependency, and VPS72 depletion suppressed proliferative programs while inducing stress, inflammatory, and apoptotic responses that were only partly shared with H2A.Z depletion. Together, these findings identify VPS72 as a recurrently altered component of tumor chromatin regulation associated with proliferative and stress-response states and support further investigation of its therapeutic significance.
SN - 1422-0067
ER -