Evidence map›Paper›PMID 40797049›Full record

ArticleNature structural & molecular biology2025

Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability.

Xiaofei Wang, Zehua Wang, Sihan Li, Dhamotharan Pattarayan, Yifei Wang, Jingchen Zhai, Yu Zhang, Haolin Wang, Meishu Xu, Junjie Zhu and 6 more

Erratum issuedAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. H3K27me3 expands the epigenetic control of piRNA transcription.Nature structural & molecular biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Xiaofei WangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-9415-5294
Zehua WangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Sihan LiCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Dhamotharan PattarayanCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-4995-1264
Yifei WangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Jingchen ZhaiDepartment of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
Yu ZhangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Haolin WangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Meishu XuCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Junjie ZhuCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Junmei WangDepartment of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0002-9607-8229
Xiaochao MaCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.ORCID http://orcid.org/0000-0003-2049-7467
Sridhar ManiDepartment of Medicine, Oncology, Molecular Pharmacology, and Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID http://orcid.org/0000-0003-4132-6157
Wen XieCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
Min ZhangDepartment of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA. miz45@pitt.edu.ORCID http://orcid.org/0000-0001-8327-6405
Da YangCenter for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA. dyang@pitt.edu.ORCID http://orcid.org/0000-0002-8336-9457

Funding

VECTOR CORE FACILITYP30CA047904 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHN C. BYRD · 1988 to 2026
$158.0M
The Center for Label-free Imagingand Multiscale Biophotonics (CLIMB)P41EB031772 · NIBIB · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Stephen A Boppart · 2022 to 2026
$7.6M
A novel lncRNA-responsive and xenobiotic receptor-mediated regulation of drug metabolism and dispositionR01CA255196 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YANG, DA · 2021 to 2025
$1.8M
The oncogenic role of EPIC1MYC axis in breast cancerR01CA222274 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI YANG, DA · 2018 to 2022
$1.8M
Enhancer RNAs Boost MYC-Chromatin Interaction to Regulate Gene Expression and TumorigenesisR01CA282704 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Da Yang · 2023 to 2026
$1.6M
LncRNA EPIC1 induces immunotherapy resistance by activating EZH2 in breast cancerR01CA272866 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Da Yang · 2023 to 2026
$1.5M
AI-Powered Biased Ligand DesignR01GM149705 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Junmei Wang · 2023 to 2026
$1.3M
High-Throughput Computing for Genomics and Bioinformatics ResearchS10OD028483 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LEE, ADRIAN V · 2021 to 2021
$574k
NCI NIH HHS P30 CA047904NCI NIH HHS R01 CA222274NCI NIH HHS R01 CA255196NCI NIH HHS R01 CA272866NCI NIH HHS R01 CA282704NIBIB NIH HHS P41 EB031772NIGMS NIH HHS R01 GM149705NIH HHS S10 OD028483
6 · The paper itself

Abstract

Pregnane X receptor (PXR) is a nuclear receptor considered to be a master transcription factor of xenobiotic metabolism. Here, using enhanced ultraviolet crosslinking and immunoprecipitation, we show that PXR can bind mRNAs in different cancer cell lines and normal liver tissues. PXR-bound mRNAs include genes related to metabolic reprogramming and lipid metabolism. Separately from its known nuclear transcriptional function, cytoplasmic PXR binds and stabilizes mature mRNA containing C+G-enriched sequences through its zinc-finger domain. Mechanistically, cytoplasmic PXR interacts with RNH1, an RNase inhibitor, to regulate RNA stability. In colorectal cancer cells, cytoplasmic PXR facilitates glucose uptake by stabilizing SLC2A1 mRNA. This process further promotes cell proliferation and cancer development. Our study unveils a previously unknown dimension of PXR-mediated gene regulation by characterizing PXR as an RNA-binding protein important for mRNA stability in the cytoplasm.

Indexed as

CytoplasmGlucosePregnane X ReceptorRNA, MessengerRNA StabilityCell Line, TumorCell ProliferationGlucose Transporter Type 1HumansProtein BindingRNA-Binding ProteinsGlucoseGlucose Transporter Type 1Pregnane X ReceptorRNA-Binding ProteinsRNA, MessengerSLC2A1 protein, human

Identifiers

PMID40797049
PMCPMC12781130

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.