Evidence map›Paper›PMID 40617410›Full record

ArticleJournal of advanced research2026

Redistribution of super-enhancers promotes malignancy in human hepatocellular carcinoma.

Jiacheng Huang, Liang Xu, Ye Chen, Mengqing Sun, Yiqing Hu, Caixu Pan, Liangyu Jiang, Menglan Wang, Jing Liu, Heng Dong and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Multi-omics integration identifiesTranslational andrology and urology · 2026
    Article
  2. Article
  3. Crosstalk BetweenCancers · 2026
    Review
  4. 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

19 authors.

Jiacheng HuangDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), China.
Liang XuCollege of Life Sciences, Zhejiang University, Hangzhou 310058, China.
Ye ChenPediatric Cancer Research Center, National Clinical Research Center for Child Health, Children's Hospital Zhejiang University School of Medicine, Hangzhou 310003, China.
Mengqing SunSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Yiqing HuDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), China.
Caixu PanDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), China.
Liangyu JiangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Menglan WangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Jing LiuSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Heng DongSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Qian LiSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Fangtian BuSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Cunjie ChangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Xuliang ChenKey Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan (Hangzhou) Hospital, Shulan International Medical College, Zhejiang Shuren University, Hangzhou 310015, China.
Yu WangSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Shusen ZhengDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), China.
Qi LingDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), China. Electronic address: lingqi@zju.edu.cn.
Jianxiang ChenSchool of Pharmacy and Department of Hepatology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China. Electronic address: chenjx@hznu.edu.cn.
Yiting QiaoDivision of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Key Laboratory of Organ Transplantation, Zhejiang Province 310003, China; Key Laboratory of the Diagnosis and Treatment of Organ Transplantation, Research Unit of Collaborative Diagnosis and Treatment For Hepatobiliary and Pancreatic Cancer, Chinese Academy of Medical Science (2019RU019), China; Institute of Organ Transplantation, Zhejiang University, Hangzhou 310003, China; State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Hangzhou 310003, China. Electronic address: yitingqiao@zju.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionSuper-enhancers (SEs) are defined as the regulatory region where intensive transcriptional cofactors bind. Dysregulation of SEs is related to multiple diseases, however, its role in hepatocellular carcinoma (HCC) remains elusive.

objectivesThis work aimed to reveal the dysregulation of SEs in HCC and the therapeutic potential for HCC treatment.

methodsFifteen HCC and twelve paracancerous samples underwent chromatin immunoprecipitation (ChIP) sequencing targeting H3K27ac, and subsequently the SEs were identified by the Rank Ordering of Super-Enhancers algorithm. Differential SEs featured by tumor or paracancerous tissues were identified, and cross-referenced with the differential expression genes and prognosis-related genes in 2 independent public or in-house HCC cohorts. The SE region of HSPA4 was deleted in the genome of HCCLM3 cell by CRISPR-Cas9, named HSPA4-SE-KO cells. The potential druggable transcriptional factors were identified by CRCmapper, GeneMANIA and Drug Gene Interaction Database (DGID).

resultsFive targets, including CDKN2C, HSPA4, GGH, PDGFA, and CAP2, were identified as HCC-gain SEs with oncogenic potential, which were further validated experimentally by SE inhibitors and ChIP targeting H3K27ac and BRD4. Cell proliferation and migration assays further confirmed that silencing of these HCC-gain SEs significantly suppressed the malignant phenotype of HCC cell lines. HSPA4 appeared strongest oncogenic functions among these targets, which was further verified by HCC mouse xenograft models and clinical sample investigation. Moreover, HSPA4-SE-KO cells obtained significantly suppressed HSPA4 expression and retarded tumorigenic capability. Finally, dysregulation of transcriptional factors engaged in the oncogenic role of SEs, and Danthron that targeting RXRA were identified from DGID for HCC treatment.

conclusionThe dysregulated SE landscape of HCC promoted the malignancy phenotype by the upregulation of oncogenes, and SE-regulatory network might be potential drug targets for HCC treatment. Our study deepened the insight of epigenetic dysregulation in HCC, offering the groundwork for SEs as potential therapeutic targets of HCC treatment.

Indexed as

Carcinoma, HepatocellularEnhancer Elements, GeneticLiver NeoplasmsAnimalsCell Line, TumorCell MovementCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansMaleMiceTranscription FactorsTranscription FactorsEpigeneticsH3K27acHepatocellular carcinomaSuper-enhancersTherapeutic targets

Identifiers

PMID40617410
PMCPMC13000944

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Registered trials

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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.