ArticleClinical and translational medicine2026
Pyrroline-5-carboxylate reductase 1 interacts with Nudix hydrolase 5 to drive bladder cancer malignant progression via activation of the APOE/JAK2/STAT3 signalling axis.
Article in Clinical and translational medicine, 2026. 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
18 authors.
Funding
Abstract
backgroundBladder cancer (BCa) is one of the most common urological malignancies, with a steadily increasing global incidence. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a metabolic regulator with noncanonical oncogenic functions; however, its protein interaction network and downstream mechanisms in BCa remain incompletely understood.
methodsPYCR1 expression and its clinical significance were evaluated using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets and tissue microarrays. Cell counting kit-8, colony formation, EdU, 3D Transwell experiments and xenograft models were used to investigate the biological functions of PYCR1. RNA sequencing, Western blot and quantitative polymerase chain reaction (qPCR) were performed to identify its downstream targets. Mass spectrometry combined with co-immunoprecipitation identified Nudix hydrolase 5 (NUDT5) as a PYCR1-interacting protein. Nuclear-cytoplasmic fractionation and adenosine triphosphate (ATP) quantification were used to measure nuclear ATP levels.
resultsPYCR1 was upregulated in BCa and promoted tumour proliferation and migration in vitro and in vivo. Mechanistically, PYCR1 interacted with NUDT5 and promoted NUDT5-dependent nuclear ATP generation. Wild-type NUDT5 restored Apolipoprotein E (APOE) expression in PYCR1-knockdown cells, whereas a catalytically inactive NUDT5 mutant failed to do so. RNA sequencing, gene set enrichment analysis, Western blot, and qPCR demonstrated that PYCR1 activated the APOE/JAK2/STAT3 signalling axis. Transcription factor prediction and dual-luciferase reporter assays identified SP1 as a transcriptional regulator of APOE. Moreover, pharmacological inhibition of NUDT5 with TH5427 suppressed BCa progression and JAK2/STAT3 activation in vitro and inhibited xenograft growth in vivo.
conclusionsPYCR1 interacts with NUDT5 to increase nuclear ATP levels, thereby sustaining SP1-dependent APOE transcription and activating JAK2/STAT3 signalling, ultimately promoting BCa progression. TH5427 may represent a promising therapeutic candidate for BCa.
Indexed as
Identifiers
What 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.