Evidence map›Paper›PMID 41159684›Full record

ArticleJournal of extracellular vesicles2025

Extracellular Vesicle-Mediated Regulation of H3C14 Contributes to Gemcitabine Resistance in Bladder Cancer.

Cheng-Shuo Huang, Dah-Shyong Yu, Shih Sheng Jiang, Ying-Si Wu, Jar-Yi Ho, Cheng-Ping Yu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of extracellular vesicles, 2025. 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
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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

6 authors.

Cheng-Shuo HuangGraduate Institute of Life Sciences, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan.ORCID https://orcid.org/0000-0002-6635-3699
Dah-Shyong YuGraduate Institute of Life Sciences, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan.
Shih Sheng JiangGraduate Institute of Life Sciences, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan.
Ying-Si WuGraduate Institute of Life Sciences, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan.
Jar-Yi HoGraduate Institute of Life Sciences, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan.
Cheng-Ping YuGraduate Institute of Life Sciences, College of Biomedical Sciences, National Defense Medical University, Taipei, Taiwan.

Funding

National Defense Medical Center MND-MAB-D-111110National Defense Medical Center MND-MAB-D-111135National Defense Medical Center MND-MAB-D-112096National Defense Medical Center MND-MAB-D-112152National Defense Medical Center MND-MAB-E-114100National Defense Medical Center MND-MAB-E-114161National Defense Medical Center MNE-MAB-E-113056National Defense Medical Center MNE-MAB-E-113182National Science and Technology Council MOST109-2314-B-016-038National Science and Technology Council MOST 109-2320-B-016-007National Science and Technology Council MOST 110-2314-B-016-064National Science and Technology Council MOST 111-2320-B-016-008-MY3National Science and Technology Council NSTC 114-2320-B-016-007National Science and Technology Council Overseas Project for Post Graduate ResearchTri-Service General Hospital TSGH-114-248Tri-Service General Hospital TSGH-E-111221Tri-Service General Hospital TSGH-E-112221Tri-Service General Hospital TSGH-E-113246
6 · The paper itself

Abstract

Extracellular vesicles (EVs) are critical mediators of intercellular communication within the tumour microenvironment and play a significant role in drug resistance. We aimed to investigate the mechanisms underlying gemcitabine (GCB) resistance in bladder cancer. GCB-resistant bladder cancer cells exhibited dysregulation of nucleoside-metabolizing enzymes and transporters. Characterization of EV subpopulations derived from GCB-resistant cells revealed their ability to transfer drug-resistant phenotypes to naïve cancer cells by modulating intracellular levels of nucleoside metabolic proteins and transporters. Proteomic and transcriptomic analyses identified the histone protein H3.2 and its corresponding transcript, H3C14, as key regulators in the transmission of GCB resistance. Notably, H3C14 overexpression in resistant cells restored GCB sensitivity, whereas its knockdown induced GCB resistance. Rab27A-mediated biogenesis and secretion emerged as a crucial mechanism regulating EV release and H3C14 excretion in GCB-resistant cells. A specific EV subpopulation enriched in CD147 and LAMB1-referred to as Excretion EVs-carried H3.2 (H3C14) but did not induce GCB resistance in recipient cells, suggesting their primary role in eliminating proteins associated with tumour progression and drug resistance. These findings highlight the role of EV-mediated H3C14 excretion in regulating GCB resistance and suggest potential therapeutic strategies targeting EV pathways to overcome drug resistance in bladder cancer.

Indexed as

DeoxycytidineDrug Resistance, NeoplasmExtracellular VesiclesHistonesUrinary Bladder NeoplasmsAntimetabolites, AntineoplasticCell Line, TumorGemcitabineHumansProteomicsTumor MicroenvironmentAntimetabolites, AntineoplasticDeoxycytidineGemcitabineHistonesextracellular vesiclesgemcitabine resistancehistone proteintumour microenvironment

Identifiers

PMID41159684
PMCPMC12570045

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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.