Evidence map›Paper›PMID 42809395›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.

Lulu Yu, Masahiko Ajiro, Vladimir Majerciak, Alexei Lobanov, Yafeng He, Maggie Cam, Baktiar Karim, Deanna Gotte, Chuxia Deng, Keji Zhao and 3 more

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 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. SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 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

13 authors.

Lulu Yu *Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702.ORCID 0000-0003-0309-9520
Masahiko Ajiro *Tumor Virus RNA Biology Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702.
Vladimir MajerciakTumor Virus RNA Biology Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702.ORCID 0000-0003-2907-4583
Alexei LobanovCenter for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, NIH, Bethesda, MD 20892.
Yafeng HeLaboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892.
Maggie CamCenter for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, NIH, Bethesda, MD 20892.
Baktiar KarimFrederick National Laboratory for Cancer Research, Frederick, MD 21702.ORCID 0000-0001-9604-9762
Deanna GotteTumor Virus RNA Biology Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702.ORCID 0009-0006-6581-8171
Chuxia DengFaculty of Synthetic Biology, Shenzhen University of Advanced Technology, Shenzhen 518107, China.
Keji ZhaoLaboratory of Epigenome Biology, Systems Biology Center, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892.ORCID 0000-0001-5559-6233
Douglas R LowyLaboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892.
Nicholas J G WebsterDepartment of Medicine, University of California San Diego, La Jolla, CA 92093.
Zhi-Ming ZhengTumor Virus RNA Biology Section, HIV Dynamics and Replication Program, Center for Cancer Research, National Cancer Institute, NIH, Frederick, MD 21702.ORCID 0000-0001-5547-7912

Funding

Gene Expression and Post-Transcriptional Regulation of DNA Tumor VirusesZIASC010357 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI ZHENG, ZHI-MING · 2009 to 2025
$24.3M
HHS | NIH | National Cancer Institute (NCI) ZIASC010357HHS | NIH | NCI | Center for Cancer Research (CCR) HHSN26120150003IIntramural NIH HHS ZIA SC010357
6 · The paper itself

Abstract

SRSF3 (SRp20) is an essential RNA splicing factor. By conditional knockout (KO) of Srsf3, we found Srsf3 at its physiological level plays a tumor-suppressive role in mouse liver carcinogenesis. Srsf3 KO in hepatocytes disrupted sex disparity in the development of DEN-induced liver cancer and resulted in high incidence of liver cancer in both male and female mice. In contrast, Srsf3 is oncogenic in the mouse mammary glands and Srsf3 KO significantly delayed the development of Erbb2 breast cancer. Srsf3 KO significantly increased the expression of transcription factors Sox4, E2f1, and Myc, calcium channel factor Trpv4, and zinc-binding Trim6 in liver cancer, but did not in Erbb2 breast cancer. Srsf3 KO enhanced the expression of glucose transmembrane transporter Mfsd4a and translation initiator Eif4a2 in DEN-induced liver cancer but reduced Mfsd4a and Eif4a2 expression in breast cancer. More importantly, Srsf3 KO reduced the expression of hepatocyte ERα and transcription factor Foxa family genes essential for sexual dimorphism in liver cancer and their downstream targets leukemia inhibitory factor receptor Lifr and epidermal growth factor receptor Egfr, but increased the expression of Myc. We further evidenced that SRSF3 binds to FOXA1 promoter and is responsible for FOXA1 promoter activity and FOXA1 expression in liver cancer cells. Together, our data highlight a functional paradigm of SRSF3 at its physiological level in tissue context-dependent gene regulation and in facilitating hepatocyte ERα and FOXA1 expression for sex disparity in liver cancer development.

Indexed as

Estrogen Receptor alphaHepatocyte Nuclear Factor 3-alphaHepatocytesLiver NeoplasmsSerine-Arginine Splicing FactorsAnimalsFemaleGene Expression Regulation, NeoplasticHumansMaleMiceMice, KnockoutSex CharacteristicsEsr1 protein, mouseEstrogen Receptor alphaFoxa1 protein, mouseHepatocyte Nuclear Factor 3-alphaSerine-Arginine Splicing FactorsSrsf3 protein, mousebreast cancergender disparityliver cancerRNA splicingSRSF3

Identifiers

PMID42809395
PMCPMC13643318

What OpenQuestion holds

Textmetadata
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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.