ZRANB1-mediated EZH2 stabilization drives S100B/S100A4 transcriptional activation and corneal neovascularization in alkali burns.
6 affiliations
- 1Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, China.
- 2Department of Ophthalmology, The First People's Hospital of Longnan, Ganzhou, Jiangxi, China.
- 3Department of Ophthalmology, First Affiliated Hospital of Jinggangshan University, Ji'an, Jiangxi, China.
- 4Department of Ophthalmology, The People's Hospital of Wanzai County, Yichun, Jiangxi, China.
- 5Department of Ophthalmology, Duchang County People's Hospital in Jiujiang City, Jiujiang, Jiangxi, China.
- 6Department of Ophthalmology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, China. [email protected].
Abstract
Alkali burn is one of the main causes of corneal injury. Corneal neovascularization caused by alkali burns aggravates corneal damage, resulting in aberrant vascular proliferation and consequent visual impairment. The present study investigated the role of enhancer of zeste homolog 2 (EZH2) in alkali burn‑induced corneal neovascularization. Through integrated bioinformatics and experimental approaches, we identified S100B, S100A4 and PI3K/AKT pathway activation as key drivers of alkali-induced corneal injury. In corneal alkali burn mice, knockdown of S100B or S100A4 attenuated corneal neovascularization and suppressed PI3K/AKT/FoxO3a pathway. EZH2 was upregulated in alkali-burn models and transcriptionally activated S100B and S100A4 via direct promoter binding. The deubiquitinase ZRANB1 was identified to stabilize EZH2 protein through deubiquitination, thereby amplifying its transcriptional activity. In alkali-injured human corneal epithelial cells, EZH2 overexpression enhanced cell viability, angiogenic capacity, migration and invasion ability, which was reversed by S100B or S100A4 knockdown. In vivo, EZH2 overexpression exacerbated PI3K/AKT/FoxO3a pathway activation and corneal neovascularization via regulating S100B or S100A4. Collectively, this study demonstrated that ZRANB1-mediated stabilization of EZH2 drove pathological corneal angiogenesis in corneal alkali burns by activating S100B/S100A4-PI3K/AKT/FoxO3a axis. These findings provided novel therapeutic targets for corneal alkali burns.
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BibTeX
@article{liu2026zranb1mediated,
title = {{ZRANB1-mediated EZH2 stabilization drives S100B/S100A4 transcriptional activation and corneal neovascularization in alkali burns.}},
author = {Fangyuan Liu and Ying Xiao and Yeping Huang and Yang Liu and Zhiyou Peng and Yulin Wang},
journal = {Biology direct},
year = {2026},
month = jul,
doi = {10.1186/s13062-026-00892-3},
url = {https://europepmc.org/article/MED/42897656},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - ZRANB1-mediated EZH2 stabilization drives S100B/S100A4 transcriptional activation and corneal neovascularization in alkali burns.
AU - Fangyuan Liu
AU - Ying Xiao
AU - Yeping Huang
AU - Yang Liu
AU - Zhiyou Peng
AU - Yulin Wang
PY - 2026
DA - 2026/07/01
JO - Biology direct
DO - 10.1186/s13062-026-00892-3
UR - https://europepmc.org/article/MED/42897656
AB - Alkali burn is one of the main causes of corneal injury. Corneal neovascularization caused by alkali burns aggravates corneal damage, resulting in aberrant vascular proliferation and consequent visual impairment. The present study investigated the role of enhancer of zeste homolog 2 (EZH2) in alkali burn‑induced corneal neovascularization. Through integrated bioinformatics and experimental approaches, we identified S100B, S100A4 and PI3K/AKT pathway activation as key drivers of alkali-induced corneal injury. In corneal alkali burn mice, knockdown of S100B or S100A4 attenuated corneal neovascularization and suppressed PI3K/AKT/FoxO3a pathway. EZH2 was upregulated in alkali-burn models and transcriptionally activated S100B and S100A4 via direct promoter binding. The deubiquitinase ZRANB1 was identified to stabilize EZH2 protein through deubiquitination, thereby amplifying its transcriptional activity. In alkali-injured human corneal epithelial cells, EZH2 overexpression enhanced cell viability, angiogenic capacity, migration and invasion ability, which was reversed by S100B or S100A4 knockdown. In vivo, EZH2 overexpression exacerbated PI3K/AKT/FoxO3a pathway activation and corneal neovascularization via regulating S100B or S100A4. Collectively, this study demonstrated that ZRANB1-mediated stabilization of EZH2 drove pathological corneal angiogenesis in corneal alkali burns by activating S100B/S100A4-PI3K/AKT/FoxO3a axis. These findings provided novel therapeutic targets for corneal alkali burns.
SN - 1745-6150
ER -