Evidence map›Paper›PMID 41071884›Full record

ArticleScience advances2025

Genome-wide CRISPR screen identifies splicing factor SF3B4 in driving hepatocellular carcinoma.

Yue Guo, Mingjing Xu, Hua Xue, Xiaofan Ding, Alissa M Wong, Na Lin, Dandan Pu, Aikha M Wong, Xin Wang, Hui Zhao and 1 more

Abstract read
In one paragraph

Article in Science advances, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. 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

11 authors.

Yue GuoDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.ORCID 0009-0001-6335-8654
Mingjing XuDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.ORCID 0000-0002-9128-1172
Hua XueDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Xiaofan DingDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao, China.
Alissa M WongDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.ORCID 0000-0001-7858-1368
Na LinDepartment of Biomedical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macao, China.ORCID 0009-0003-4256-5915
Dandan PuDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.ORCID 0009-0009-6939-9287
Aikha M WongDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
Xin WangDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.ORCID 0000-0002-5122-2418
Hui ZhaoKey Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China.ORCID 0000-0001-8160-6415
Nathalie WongDepartment of Surgery, Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China.ORCID 0000-0003-2397-9189

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Although genome sequencings have recognized many cancer-associated genes in hepatocellular carcinoma (HCC), distinguishing their functional effect remains challenging. Leveraging on a genome-wide CRISPR knockout (KO) screening, we uncovered spliceosome factors as major survival essential genes in HCC and up-regulations of ferroptosis suppressors [particularly glutamate-cysteine ligase catalytic subunit (GCLC)] in lenvatinib resistance. Our KO screen in patient-derived HCC organoid showed splicing factor 3b subunit 4 (SF3B4) to be top-ranked, conferring prosurvival signal in HCC organoid and driving tumorigenic potentials in both hepatic progenitor organoids and hydrodynamic tail vein injection HCC murine model. The combined RNA immunoprecipitation sequencing, long-read isoform sequencing, and transcriptome revealed characteristic splicing landscape regulated by SF3B4 and identified T-box transcription factor 3 (TBX3) variant TBX3+2a as a potent downstream effector. Our findings highlighted vital roles of SF3B4 in HCC cell survival and tumor progression, and the phenomenon of ferroptosis resistance in patients unresponsive to first-line agent lenvatinib.

Indexed as

Carcinoma, HepatocellularClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsLiver NeoplasmsRNA Splicing FactorsAnimalsCell Line, TumorDrug Resistance, NeoplasmFerroptosisGene Expression Regulation, NeoplasticHumansMicePhenylurea CompoundsQuinolinesT-Box Domain ProteinslenvatinibPhenylurea CompoundsQuinolinesRNA Splicing FactorsT-Box Domain Proteins

Identifiers

PMID41071884
PMCPMC12513437

What OpenQuestion holds

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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.