ArticleInternational ophthalmology2025
USP39 promotes retinal pathological angiogenesis in retinopathy of prematurity by stabilizing SIRT2 expression through deubiquitination.
Article in International ophthalmology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRetinopathy of prematurity (ROP) is a major cause of childhood blindness worldwide, highlighted by retinal neovascularization. Ubiquitin is present throughout the retina. The deubiquitinating enzyme ubiquitin-specific protease 39 (USP39) has been reported to be involved in angiogenesis. Here, this study aimed to investigate the effects of USP39 on ROP and its associated mechanism.
methodsHypoxia-induced human retinal microvascular endothelial cells (hRMECs) were adopted for functional analyses. Detection of mRNA and protein was conducted using quantitative real-time PCR and western blotting. Cell migration, invasion and angiogenesis were evaluated using transwell and tube formation assays. Protein interaction was determined by immunoprecipitation assay. Oxygen-induced retinopathy (OIR) mouse models were used for in vivo analysis.
resultsUSP39 level was higher in hypoxia-induced hRMECs, functionally, USP39 silencing reversed hypoxia-induced migration, invasion and angiogenesis in hRMECs. In further mechanism analysis, we found that USP39 stabilized SIRT2 protein expression in hRMECs by inducing SIRT2 deubiquitination. Moreover, SIRT2 up-regulation abated hypoxia-evoked migration, invasion and angiogenesis in hRMECs. Besides that, the inhibitory effects of USP39 silencing on hypoxia-induced metastatic and angiogenic behaviors were abolished after SIRT2 overexpression. In addition, USP39 silencing blocked the activation of phosphoinositide 3-kinase (PI3K)/protein kinase B pathway (AKT) by regulating SIRT2. In vivo assay showed that levels of USP39, SIRT2, matrix metalloproteinase (MMP)-2 (MMP-2), MMP-9 and Vascular endothelial growth factor A (VEGFA) were increased in the retinas of OIR mice, while intravitreal injection of USP39 short hairpin RNA (shRNA) could reduce their expression.
conclusionUSP39 stabilized SIRT2 expression by deubiquitination and promoted hypoxia-induced metastatic and angiogenic behaviors of RMECs in vitro, as well as retinal angiogenesis in vivo.
Indexed as
Identifiers
39853525What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.