Evidence map›Paper›PMID 39281020›Full record

ArticleJournal of extracellular biology2024

5-Fluorouracil treatment represses pseudouridine-containing miRNA export into extracellular vesicles.

Shimian Qu, Hannah M Nelson, Xiao Liu, Yu Wang, Elizabeth M Semler, Danielle L Michell, Clark Massick, Jeffrey L Franklin, John Karijolich, Alissa M Weaver and 4 more

Abstract read
In one paragraph

Article in Journal of extracellular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Pseudouridine synthase 7 as a context-specific therapeutic target in cancer.The Journal of pharmacology and experimental therapeutics · 2026
    Review
  3. Review
  4. Pseudouridine selects RNAs for extracellular transport.bioRxiv : the preprint server for biology · 2025
    Article
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Shimian QuDepartment of Biological Sciences Vanderbilt University Nashville Tennessee USA.ORCID https://orcid.org/0009-0002-1886-7844
Hannah M NelsonDepartment of Biological Sciences Vanderbilt University Nashville Tennessee USA.
Xiao LiuCenter for Extracellular Vesicle Research Vanderbilt University and Vanderbilt University Medical Center Nashville Tennessee USA.
Yu WangCenter for Extracellular Vesicle Research Vanderbilt University and Vanderbilt University Medical Center Nashville Tennessee USA.
Elizabeth M SemlerDepartment of Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Danielle L MichellDepartment of Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Clark MassickDepartment of Medicine Vanderbilt University Medical Center Nashville Tennessee USA.
Jeffrey L FranklinCenter for Extracellular Vesicle Research Vanderbilt University and Vanderbilt University Medical Center Nashville Tennessee USA.
John KarijolichDepartment of Pathology, Microbiology and Immunology Vanderbilt University Nashville Tennessee USA.
Alissa M WeaverCenter for Extracellular Vesicle Research Vanderbilt University and Vanderbilt University Medical Center Nashville Tennessee USA.ORCID https://orcid.org/0000-0002-4096-8636
Robert J CoffeyCenter for Extracellular Vesicle Research Vanderbilt University and Vanderbilt University Medical Center Nashville Tennessee USA.ORCID https://orcid.org/0000-0002-2180-3844
Qi LiuCenter for Extracellular Vesicle Research Vanderbilt University and Vanderbilt University Medical Center Nashville Tennessee USA.
Kasey C VickersCenter for Extracellular Vesicle Research Vanderbilt University and Vanderbilt University Medical Center Nashville Tennessee USA.
James G PattonDepartment of Biological Sciences Vanderbilt University Nashville Tennessee USA.

Funding

Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MARY Kay WASHINGTON · 2002 to 2026
$29.9M
Non-coding RNA & Bioinformatics CoreP01HL116263 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI KON, VALENTINA · 2014 to 2025
$24.7M
Vanderbilt-Ingram Cancer Center SPORE in Gastrointestinal CancerP50CA236733 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STEPHEN W. FESIK · 2019 to 2026
$19.6M
Roles for Supermeres in CRC ProgressionP01CA229123 · NCI · VANDERBILT UNIVERSITY · PI Alissa M Weaver · 2020 to 2026
$12.9M
Integrated approach to study early and late events in colonic neoplasia: mouse to manR35CA197570 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Robert J. Coffey · 2017 to 2026
$9.4M
Uncovering exRNA and protein determinants of secreted vesicle heterogeneity by flow cytometric purification of vesicle subsets from cells and plasmaUH3CA241685 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CHAREST, ALAIN, COFFEY, ROBERT J. · 2021 to 2022
$2.1M
Novel functions of plasminogen and its diverse cargo in bloodR01HL173598 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kasey C Vickers · 2024 to 2026
$1.1M
American Heart Association-American Stroke Association 971070NCI NIH HHS P01 CA229123NCI NIH HHS P50 CA236733NCI NIH HHS R35 CA197570NCI NIH HHS UH3 CA241685NHLBI NIH HHS P01 HL116263NHLBI NIH HHS R01 HL173598NIDDK NIH HHS P30 DK058404
6 · The paper itself

Abstract

5-Fluorouracil (5-FU) has been used for chemotherapy for colorectal and other cancers for over 50 years. The prevailing view of its mechanism of action is inhibition of thymidine synthase leading to defects in DNA replication and repair. However, 5-FU is also incorporated into RNA causing defects in RNA metabolism, inhibition of pseudouridine modification, and altered ribosome function. We examined the impact of 5-FU on post-transcriptional small RNA modifications (PTxMs) and the expression and export of RNA into small extracellular vesicles (sEVs). EVs are secreted by all cells and contain a variety of proteins and RNAs that can function in cell-cell communication. We found that treatment of colorectal cancer (CRC) cells with 5-FU represses sEV export of miRNA and snRNA-derived RNAs, but promotes export of snoRNA-derived RNAs. Strikingly, 5-FU treatment significantly decreased the levels of pseudouridine on both cellular and sEV small RNA profiles. In contrast, 5-FU exposure led to increased levels of cellular small RNAs containing a variety of methyl-modified bases. These unexpected findings show that 5-FU exposure leads to altered RNA expression, base modification, and aberrant trafficking and localization of small RNAs.

Indexed as

5‐FUEV exportextracellular vesiclesmiRNApseudourineRNA modification

Identifiers

PMID39281020
PMCPMC11393769

What OpenQuestion holds

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Registered trials

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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.