Evidence map›Paper›PMID 38944674›Full record

ArticleJournal of extracellular vesicles2024

Oxidative stress induces extracellular vesicle release by upregulation of HEXB to facilitate tumour growth in experimental hepatocellular carcinoma.

Jiufei Duan, Zhao Huang, Siyuan Qin, Bowen Li, Zhe Zhang, Rui Liu, Kui Wang, Edouard C Nice, Jingwen Jiang, Canhua Huang

Abstract read
In one paragraph

Article in Journal of extracellular vesicles, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing 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

23 citing papers in PubMed.

  1. Article
  2. Review
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  4. Article
  5. Review
  6. Diagnostic and prognostic significance of circulating extracellular vesicles in gastrointestinal cancers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Article
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  13. Article
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  16. Review
  17. Molecular mechanisms of mitochondrial quality control.Translational neurodegeneration · 2025
    Review
  18. Review
  19. Article
  20. Review
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

10 authors.

Jiufei DuanDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, P.R. China.ORCID https://orcid.org/0000-0001-8497-2779
Zhao HuangWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, P.R. China.
Siyuan QinDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, P.R. China.
Bowen LiDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, P.R. China.
Zhe ZhangMOE Joint International Research Laboratory of Pancreatic Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Rui LiuState Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Research Unit of Oral Carcinogenesis and Management, Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, P.R. China.
Kui WangDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, P.R. China.
Edouard C NiceDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Jingwen JiangWest China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, P.R. China.
Canhua HuangDepartment of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, P.R. China.ORCID https://orcid.org/0000-0003-2247-7750

Funding

1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University ZYGD220071·3·5 project for disciplines of excellence, West China Hospital, Sichuan University ZYJC21004Guangdong Basic and Applied Basic Research Foundation 2019B030302012National Key Research and Development Project of China 2020YFA0509400National Key Research and Development Project of China 2023YFC3402100National Natural Science Foundation of China 81821002National Natural Science Foundation of China 82130082National Natural Science Foundation of China 82303838National Natural Science Foundation of China 82341004
6 · The paper itself

Abstract

Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains poorly understood. Here, we demonstrate the involvement of β-hexosaminidase B (HEXB) in mediating EV release in response to oxidative stress, thereby promoting the development of hepatocellular carcinoma (HCC). Mechanistically, reactive oxygen species (ROS) stimulate the nuclear translocation of transcription factor EB (TFEB), leading to the upregulation of both HEXB and its antisense lncRNA HEXB-AS. HEXB-AS can bind HEXB to form a protein/RNA complex, which elevates the protein stability of HEXB. The stabilized HEXB interacts with lysosome-associated membrane glycoprotein 1 (LAMP1), disrupting lysosome-multivesicular body (MVB) fusion, which protects EVs from degradation. Knockdown of HEXB efficiently inhibits EV release and curbs HCC growth both in vitro and in vivo. Moreover, targeting HEXB by M-31850 significantly inhibits HCC growth, especially when combined with GW4869, an inhibitor of exosome release. Our results underscore the critical role of HEXB as a modulator that promotes EV release during HCC development.

Indexed as

Carcinoma, HepatocellularExtracellular VesiclesLiver NeoplasmsOxidative StressAnimalsCell Line, TumorCell ProliferationGene Expression Regulation, NeoplasticHumansMaleMiceMice, NudeReactive Oxygen SpeciesRNA, Long NoncodingUp-RegulationReactive Oxygen SpeciesRNA, Long NoncodingEV secretionhepatocellular carcinomalysosomeβ‐hexosaminidase B (HEXB)

Identifiers

PMID38944674
PMCPMC11214608

What OpenQuestion holds

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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.