Evidence map›Paper›PMID 35848447›Full record

ArticleCancer communications (London, England)2022

The E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress glioblastoma progression.

Ye Yuan, Li-Hong Wang, Xian-Xian Zhao, Jiao Wang, Meng-Si Zhang, Qing-Hua Ma, Sen Wei, Ze-Xuan Yan, Yue Cheng, Xiao-Qing Chen and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cancer communications (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.9field-weighted citation impact, top 14% of its field
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

17 citing papers in PubMed, 23 citations in OpenAlex.

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  10. [ORY-1001 inhibits glioblastoma cell growth by downregulating the Notch/HES1 pathwayNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024
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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

17 authors at 3 institutions in 2 countries.

Ye YuanInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Li-Hong WangInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Xian-Xian ZhaoDepartment of Clinical Laboratory, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, P. R. China.
Jiao WangInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Meng-Si ZhangInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Qing-Hua MaInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Sen WeiInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Ze-Xuan YanInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Yue ChengInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Xiao-Qing ChenInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Hong-Bo ZouDepartment of Oncology, the Third Affiliated Hospital of Chongqing Medical University, Chongqing, 401120, P. R. China.
Jia GeInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Yan WangInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Xia ZhangInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
You-Hong CuiInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Tao LuoInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Xiu-Wu BianInstitute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, P. R. China.
Army Medical University · CNSouthwest General Health Center · USThe Affiliated Yongchuan Hospital of Chongqing Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundElucidation of the post-transcriptional modification has led to novel strategies to treat intractable tumors, especially glioblastoma (GBM). The ubiquitin-proteasome system (UPS) mediates a reversible, stringent and stepwise post-translational modification which is closely associated with malignant processes of GBM. To this end, developing novel therapeutic approaches to target the UPS may contribute to the treatment of this disease. This study aimed to screen the vital and aberrantly regulated component of the UPS in GBM. Based on the molecular identification, functional characterization, and mechanism investigation, we sought to elaborate a novel therapeutic strategy to target this vital factor to combat GBM.

methodsWe combined glioma datasets and human patient samples to screen and identify aberrantly regulated E3 ubiquitin ligase. Multidimensional database analysis and molecular and functional experiments in vivo and in vitro were used to evaluate the roles of HECT, UBA and WWE domain-containing E3 ubiquitin ligase 1 (HUWE1) in GBM. dCas9 synergistic activation mediator system and recombinant adeno-associated virus (rAAV) were used to endogenously overexpress full-length HUWE1 in vitro and in glioma orthotopic xenografts.

resultsLow expression of HUWE1 was closely associated with worse prognosis of GBM patients. The ubiquitination and subsequent degradation of N-Myc mediated by HUWE1, leading to the inactivation of downstream Delta-like 1 (DLL1)-NOTCH1 signaling pathways, inhibited the proliferation, invasion, and migration of GBM cells in vitro and in vivo. A rAAV dual-vector system for packaging and delivery of dCas9-VP64 was used to augment endogenous HUWE1 expression in vivo and showed an antitumor activity in glioma orthotopic xenografts.

conclusionsThe E3 ubiquitin ligase HUWE1 acts through the N-Myc-DLL1-NOTCH1 signaling axis to suppress GBM progression. Antitumor activity of rAAV dual-vector delivering dCas9-HUWE1 system uncovers a promising therapeutic strategy for GBM.

Indexed as

GlioblastomaTumor Suppressor ProteinsUbiquitin-Protein LigasesCalcium-Binding ProteinsHumansMembrane ProteinsN-Myc Proto-Oncogene ProteinReceptor, Notch1Signal TransductionUbiquitinationCalcium-Binding ProteinsDLK1 protein, humanHUWE1 protein, humanMembrane ProteinsMYCN protein, humanN-Myc Proto-Oncogene ProteinNOTCH1 protein, humanReceptor, Notch1Tumor Suppressor ProteinsUbiquitin-Protein LigasesDLL1E3 ubiquitin ligaseglioblastomaHUWE1N-MycNOTCH1recombinant adeno-associated virusubiquitin-proteasome system

Identifiers

PMID35848447
PMCPMC9456703
OpenAlexW4285730423

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.