Evidence map›Paper›PMID 41761910›Full record

ArticleNucleic acids research2026

FOXN3 integrates the KU70/KU80/SREBP-1 complex to regulate lipid metabolism in non-alcoholic fatty liver disease.

Jiang Du, Lele Jin, Suhui Wang, Xinghong Hu, Jinjin Yu, Jingyu Yu, Qingyang Huo, Nan Wu, Xiaotian Liu, Yan Yang and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Jiang DuAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Lele JinAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Suhui WangAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Xinghong HuAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Jinjin YuMolecular Diagnosis Center, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Jingyu YuResearch Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu 233004, China.
Qingyang HuoAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Nan WuMolecular Diagnosis Center, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Xiaotian LiuResearch Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu 233004, China.
Yan YangDepartment of Medical Oncology, The First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China.
Yong ZhangAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.
Sizhou HuangDevelopment and Regeneration Key Laboratory of Sichuan Province, Department of Anatomy and Histology and Embryology, School of Basic Medical Sciences, Chengdu Medical College, Chengdu 610500, China.ORCID 0000-0002-8331-1933
Jihong ZhouResearch Center of Clinical Laboratory Science, School of Laboratory Medicine, Bengbu Medical University, Bengbu 233004, China.
Song Guo ZhengDepartment of Immunology, the School of Cell and Gene Therapy, Songjiang Research Institute and Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Chunfu ZhengDepartment of Microbiology, Immunology & Infection Diseases, University of Calgary, Calgary, Alberta T2N 4N1, Canada.ORCID 0000-0002-8797-1322
Xinxing ZhuAnhui Province Key Laboratory of Respiratory Tumor and Infectious Disease, Department of Respiratory and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical University, Bengbu 233004, China.ORCID 0000-0002-8705-0013

Funding

Clinical Medical Research 202304295107020074First Affiliated Hospital of Bengbu Medical University 2025byyfyjq03National Natural Science Foundation of China 82402634Natural Science Foundation of Anhui Province 2508085Y055
6 · The paper itself

Abstract

The sterol regulatory element-binding transcription factor 1 (SREBP-1) plays a crucial role in the transcriptional regulation of lipogenic response genes, thereby contributing to the development of non-alcoholic fatty liver disease (NAFLD). However, the modulation of SREBP-1 transcriptional activity remains incompletely understood. Here, we report that the transcription factor FOXN3 interacts with the KU70/KU80/SREBP-1 complex, facilitating the recruitment of SREBP-1 for the transcriptional activation of lipogenic response genes. Hepatocyte-specific knockout of FOXN3 significantly alleviates the pathological progression of NAFLD by suppressing fatty acid and cholesterol synthesis. Furthermore, phosphorylation of FOXN3 at the S83 and S85 residues disrupts the stability of the KU70/KU80/FOXN3/SREBP-1 complex, which is required for SREBP-1 transcriptional activity. This disruption consequently impedes the progression of NAFLD. Clinical investigations reveal that FOXN3, KU80, and SREBP-1 co-target the promoters of lipogenic response genes in fatty liver tissues from patients. Notably, phosphorylation levels of FOXN3 at S83 and S85 are significantly reduced in fatty liver tissues compared to normal samples. This reduction enhances the enrichment of the FOXN3/SREBP-1 complex at the promoters of lipogenic response genes during the progression of NAFLD. Our study underscores the critical role of FOXN3 in maintaining the intact KU70/KU80/FOXN3/SREBP-1 complex, which is essential for SREBP-1-mediated metabolic disorders.

Indexed as

Forkhead Transcription FactorsKu AutoantigenLipid MetabolismNon-alcoholic Fatty Liver DiseaseSterol Regulatory Element Binding Protein 1AnimalsHepatocytesHumansLiverMicePhosphorylationForkhead Transcription FactorsKu AutoantigenSREBF1 protein, humanSterol Regulatory Element Binding Protein 1Xrcc6 protein, humanXrcc6 protein, mouse

Identifiers

PMID41761910
PMCPMC12956355

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.