Evidence map›Paper›PMID 40682778›Full record

ArticleCell reports2025

Coordinated expression of retained introns and poison exons in renal cell carcinoma.

José C Martínez, Mi Zhou, Gilbert Giri, Yi-Hsuan Tsai, Meghan M Rowley, Grant A Goda, Maria M Aleman, William Y Kim, Daniel Dominguez

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

José C MartínezLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Hematology, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Mi ZhouLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Gilbert GiriDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, USA.
Yi-Hsuan TsaiLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Meghan M RowleyDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Grant A GodaDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Chemistry, University of North Carolina, Chapel Hill, NC, USA.
Maria M AlemanDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; RNA Discovery Center, University of North Carolina, Chapel Hill, NC, USA.
William Y KimLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Division of Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: wykim@med.unc.edu.
Daniel DominguezLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, USA; RNA Discovery Center, University of North Carolina, Chapel Hill, NC, USA. Electronic address: didoming@email.unc.edu.

Funding

UNC Oncology K12K12CA120780 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLIAM Y. KIM · 2007 to 2026
$9.6M
UNC Integrated Translational Oncology Program (UNC-iTOP)T32CA244125 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WILLIAM Y. KIM, Jen Jen Yeh · 2019 to 2026
$3.9M
Protein Disorder as a Modifier of RNA Binding and RegulationR35GM142864 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Daniel Issac Dominguez · 2021 to 2026
$2.5M
Triggering Aberrant RNA Processing for RCC TherapyR01CA290597 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Daniel Issac Dominguez, WILLIAM Y. KIM · 2024 to 2026
$1.9M
UNC Immunotherapy Training Grant (IM-TAG)T32CA285257 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Jonathan S. Serody · 2023 to 2026
$668k
NCI NIH HHS K12 CA120780NCI NIH HHS R01 CA290597NCI NIH HHS T32 CA244125NCI NIH HHS T32 CA285257NIGMS NIH HHS R35 GM142864
6 · The paper itself

Abstract

The regulation and impact of tumor-specific isoforms in cancer is challenging to understand, with unclear links between oncogenic signaling and mRNA processing and decay. Using transcriptomic analyses and experimental validation, we demonstrate that clear cell renal cell carcinoma (ccRCC) tumors exhibit coordinated intron retention (IR) and poison exon (PE) inclusion, generating transcripts targeted by nonsense-mediated decay (NMD). ccRCC tumors segregate into two subtypes based on IR: tumors with low IR levels and those with high IR levels, the latter associated with aggressive clinical features and poorer survival. We identify mammalian target of rapamycin (mTOR) signaling as a key modulator of IR and PE inclusion, showing mTOR inhibition significantly increases NMD-targeted isoforms, linking mTOR signaling with RNA surveillance pathways. Additionally, tumors with high IR levels exhibit increased T cell infiltration signatures. Collectively, these findings reveal a mechanism by which aggressive ccRCC tumors sustain aberrant RNA isoforms, offering insights for biomarker and therapeutic development.

Indexed as

Carcinoma, Renal CellExonsGene Expression Regulation, NeoplasticIntronsKidney NeoplasmsCell Line, TumorHumansNonsense Mediated mRNA DecaySignal TransductionTOR Serine-Threonine KinasesTOR Serine-Threonine Kinasescancer genomicsclear cell renal cell carcinomaCP: CancerCP: Genomicsimmunotherapyintron retentionmTORnonsense-mediated decaypoison exons

Identifiers

PMID40682778
PMCPMC12809107

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.