Evidence map›Paper›PMID 42303814›Full record

ArticleNature biomedical engineering2026

Programmable mRNA 3'UTR engineering restores MHC-I and overcomes immune evasion in prostate cancer.

Furong Huang, Fuwen Yuan, Kexin Li, Ya Cui, Lei Li, Wenbin Ye, Zhifen Cui, Jingyue Yan, Qiang Chen, Christopher Nicchitta and 13 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature biomedical engineering, 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. 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

23 authors.

Furong Huang *Department of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.
Fuwen Yuan *Department of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0001-5764-2504
Kexin Li *Department of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.
Ya Cui *Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0003-1574-0928
Lei Li *Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0003-3924-2544
Wenbin Ye *Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA.ORCID http://orcid.org/0000-0002-7811-2710
Zhifen CuiDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-5223-930X
Jingyue YanDepartment of Immunology and Immunotherapy and Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Qiang ChenDepartment of Cell Biology, Duke University School of Medicine, Durham, NC, USA.
Christopher NicchittaDepartment of Cell Biology, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0001-7889-1155
Yuebao ZhangDivision of Pharmaceutics and Pharmacology, College of Pharmacy, Ohio State University, Columbus, OH, USA.ORCID http://orcid.org/0009-0000-7883-1937
William HankeyDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.
Jeffrey EverittDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0273-6284
Kai-Lieh HuangDepartment of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
Mu-En WangDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-5953-3499
Ming ChenDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-3470-1062
Jiaoti HuangDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-1195-1998
Hongyan WangDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA.
Eric J WagnerDepartment of Biochemistry and Biophysics, Center for RNA Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.ORCID http://orcid.org/0000-0003-0217-383X
Xin LuDepartment of Biological Sciences, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, USA.ORCID http://orcid.org/0000-0002-0284-6478
Yizhou DongDepartment of Immunology and Immunotherapy and Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. yizhou.dong@mssm.edu.ORCID http://orcid.org/0000-0001-5786-0659
Wei LiDivision of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA. wei.li@uci.edu.ORCID http://orcid.org/0000-0001-9931-5990
Qianben WangDepartment of Pathology and Duke Cancer Institute, Duke University School of Medicine, Durham, NC, USA. qianben@ibms.pumc.edu.cn.ORCID http://orcid.org/0000-0003-2636-7145

Funding

Elucidating alternative polyadenylation regulation during prostate cancer progression to castration-resistanceR01CA290720 · NCI · DUKE UNIVERSITY · PI Jiaoti Huang, Wei Li · 2024 to 2026
$2.0M
NCI NIH HHS R01 CA290720U.S. Department of Defense (United States Department of Defense) W81XWH-20-1-0068
6 · The paper itself

Abstract

Immune-cold tumours such as prostate cancer often resist immune checkpoint therapies (ICT) due to impaired antigen presentation via major histocompatibility complex class I (MHC-I). While MHC-I downregulation is a common immune evasion mechanism, no approved therapies selectively restore MHC-I expression in tumours. We developed a programmable RNA engineering platform, termed the 3'UTR CRISPR/dCas13 Engineering System (3'UTRCES), to precisely manipulate mRNA alternative polyadenylation (APA) in vivo. We identified tumour-specific 3'UTR shortening of the E3 ligase adaptor SPSB1 as a driver of MHC-I degradation via SPSB1-mediated ubiquitination, without affecting PD-L1. Lipid nanoparticle (LNP)-delivered 3'UTRCES reversed SPSB1 3'UTR shortening, restored MHC-I expression and sensitized tumours to ICT in syngeneic mice. These effects were elicited by MHC-I-dependent increases in CD8 T cell infiltration and antitumour cytotoxic activity. Our findings reveal APA-driven MHC-I suppression as a previously unrecognized mechanism of immune escape and establish LNP-3'UTRCES as a versatile platform for post-transcriptional RNA engineering in cancer.

Identifiers

PMID42303814
PMCPMC13297525

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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.