Evidence map›Paper›PMID 41462308›Full record

ArticleJournal of experimental & clinical cancer research : CR2025

TCF3 activates super-enhancer-driven TRIB2 overexpression to suppress ferroptosis and promote hepatoblastoma proliferation.

Han Wu, Guoqing Zhu, Qianshu Zhu, Ji Ma, Siwei Mao, Miao Ding, Jiabei Zhu, Xiaochen Tang, Zhixuan Bian, Yuhua Shan and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. 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

14 authors.

Han Wu *Department of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Guoqing Zhu *Department of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Qianshu Zhu *Chongqing Key Laboratory of Human Embryo Engineering and Precision Medicine, NHC Key Laboratory of Birth Defects and Reproductive Health, Center for Reproductive Medicine, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.
Ji MaDepartment of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Siwei MaoDepartment of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Miao DingDepartment of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Jiabei ZhuDepartment of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Xiaochen TangDepartment of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Zhixuan BianDepartment of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China.
Yuhua ShanDepartment of Oncology Surgery, International Diagnosis and Treatment (Special Consultation) Department, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Song GuDepartment of Oncology Surgery, International Diagnosis and Treatment (Special Consultation) Department, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Fenyong SunDepartment of Clinical Laboratory, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Middle Yanchang Road No.301, Jing'an District, Shanghai, 200072, China. sunfenyong@263.net.
Cizhong JiangKey Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Siping Road No.1239, Yangpu District, Shanghai, 200092, China. czjiang@tongji.edu.cn.
Qiuhui PanDepartment of Clinical Laboratory, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Dongfang Road No.1678, Pudong New District, Shanghai, 200127, China. panqiuhui_med@163.com.

Funding

Leading Talents in Health Care of Shanghai Municipal Health Commission 2022LJ020National Natural Science Foundation of China 82293662National Natural Science Foundation of China 82372701National Natural Science Foundation of China 82402711Sanya Science and Technology Special Fund 2022KJCX38Shanghai Key Laboratory of Clinical Molecular Diagnostics for Pediatrics 20dz2260900
6 · The paper itself

Abstract

backgroundHepatoblastoma (HB) is the most common pediatric liver malignancy with an increasing incidence. However, the functional roles of 3D chromatin organization, epigenetic regulatory factors, and transcriptional reprogramming in HB pathogenesis remain poorly understood.

methods​Integrated multi-omics analyses of HB and matched non-tumor tissues were performed, including Hi-C, H3K27ac CUT&Tag, ATAC-seq, and RNA-seq, to construct high-resolution 3D epigenomic maps and identify genes interacting with HB-specific super-enhancers (SEs). Functional assays of identified targets were conducted in cell lines and animal models. The regulatory mechanisms of SEs and upstream transcription factors (TFs) were investigated using CRISPRi-dCas9, 3C-qPCR, ChIP-qPCR, and luciferase reporter assays.

resultsComprehensive analysis identified TRIB2 as an HB-specific SE-associated oncogene. Functionally, TRIB2 promoted cell proliferation and accelerated tumor growth both in vitro and in vivo. Patients with high TRIB2 expression exhibited advanced PRETEXT stage and metastasis. Mechanistically, TCF3 directly bound to both the TRIB2-SE and its promoter, promoting TRIB2 overexpression. Moreover, TRIB2 conferred resistance to ferroptosis by disrupting KEAP1-mediated ubiquitination of NRF2, thereby stabilizing NRF2 protein and enhancing antioxidant responses. The TCF3-TRIB2-NRF2 axis showed significant co-expression in HB tissues, effectively distinguished HB from normal liver tissues, and was associated with poorer overall survival.

conclusionsOur findings reveal that TCF3 and SE mediate TRIB2 overexpression to inhibit ferroptosis via the KEAP1-NRF2 pathway and drive HB pathogenesis, providing potential diagnostic and prognostic markers for HB.

Indexed as

Basic Helix-Loop-Helix ProteinsFerroptosisHepatoblastomaIntracellular Signaling Peptides and ProteinsLiver NeoplasmsAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell Line, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMaleMiceBasic Helix-Loop-Helix ProteinsCalcium-Calmodulin-Dependent Protein KinasesIntracellular Signaling Peptides and ProteinsTCF3 protein, humanTRIB2 protein, humanEpigeneticsHepatoblastomaHi-CKEAP1Multi-omicsNRF2Reactive oxygen speciesSuper-enhancerTRIB2

Identifiers

PMID41462308
PMCPMC12750601

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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.