Evidence map›Paper›PMID 42161938›Full record

ArticleNature communications2026

microRNA-25 drives immune checkpoint therapy resistance by repressing innate and humoral immunity via Syndecan-3.

Zhouting Zhu, Wenyan Han, Yufei Deng, Zhaoyang Jia, Gulshanbir Baidwan, Lujing Wu, Shweta Jakhmola, Tongyun Wang, Dhenugen Logeswaran, Jing Wen and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. 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. TheNon-coding RNA · 2026
    Article
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

18 authors.

Zhouting ZhuDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.ORCID http://orcid.org/0000-0001-7763-486X
Wenyan HanDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Yufei DengDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Zhaoyang JiaDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.ORCID http://orcid.org/0009-0000-4531-1142
Gulshanbir BaidwanDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Lujing WuDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Shweta JakhmolaDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Tongyun WangDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Dhenugen LogeswaranDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Jing WenDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.ORCID http://orcid.org/0009-0001-4627-4598
Amanda Y SunDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Bill BrayDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Na LiDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.ORCID http://orcid.org/0000-0002-2852-8099
Lingling WangDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Hui HuiDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA.
Jiaqian WuGraduate School of Biomedical Sciences, Sanford Burnham Prebys Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, California, USA.
Sandip Pravin PatelMoores Cancer Center, 3855 Health Sciences Drive, University of California San Diego, La Jolla, California, USA.
Tariq M RanaDepartment of Cellular and Molecular Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, California, USA. trana@ucsd.edu.ORCID http://orcid.org/0000-0001-9558-5766

Funding

Virology CoreP01CA177322 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WU, TING-TING · 2014 to 2018
$8.7M
NCI NIH HHS P01 CA177322U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) CA177322
6 · The paper itself

Abstract

Immune checkpoint therapy (ICT) can induce durable tumor control but is limited by primary and acquired resistance. The mechanisms underlying immune-resistant tumor microenvironments (TMEs) remain incompletely understood. Here we show that deletion of microRNA-25 (miR-25) sensitizes tumors to ICT across multiple syngeneic mouse models. Single-cell transcriptomics reveals that miR-25 deficiency activates innate and humoral immunity by increasing major histocompatibility complex class II (MHC II) expression in tumor-associated macrophages (TAMs) and enhancing classical complement signaling in cancer-associated fibroblasts (CAFs). Complement activation shifts CAFs toward an inflammatory (iCAF) state, reduces suppressive crosstalk with TAMs, and promotes a pro-inflammatory TME. Mechanistically, miR-25 represses Syndecan-3 (SDC3) in response to interferon-γ (IFN-γ). Editing the miR-25 binding site in Sdc3 restores SDC3 expression and overcomes resistance. These findings identify miR-25-mediated SDC3 repression as a driver of immune resistance and suggest strategies to convert immune-cold tumors into ICT-responsive hot tumors, offering avenues to enhance ICT.

Indexed as

Drug Resistance, NeoplasmImmunity, HumoralImmunity, InnateMicroRNAsNeoplasmsSyndecan-3AnimalsCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansInterferon-gammaMacrophagesMiceMice, Inbred C57BLMice, KnockoutInterferon-gammaMicroRNAsMIRN25 microRNA, humanSyndecan-3

Identifiers

PMID42161938
PMCPMC13381856

What OpenQuestion holds

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LicenceCC BY
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.