Evidence map›Paper›PMID 34571917›Full record

ArticleCells2021

Overexpression of the Ubiquitin Specific Proteases USP43, USP41, USP27x and USP6 in Osteosarcoma Cell Lines: Inhibition of Osteosarcoma Tumor Growth and Lung Metastasis Development by the USP Antagonist PR619.

Mélanie Lavaud, Mathilde Mullard, Robel Tesfaye, Jérôme Amiaud, Mélanie Legrand, Geoffroy Danieau, Régis Brion, Sarah Morice, Laura Regnier, Maryne Dupuy and 5 more

Open access · goldAbstract read
In one paragraph

Article in Cells, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
3.4field-weighted citation impact, top 6% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. AKT and DUBs: a bidirectional relationship.Cellular & molecular biology letters · 2025
    Review
  5. Role of the USP family in autophagy regulation and cancer progression.Apoptosis : an international journal on programmed cell death · 2025
    Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. 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

15 authors at 1 institution in 1 country.

Mélanie LavaudINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Mathilde MullardINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Robel TesfayeINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.ORCID 0000-0003-2358-219X
Jérôme AmiaudINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Mélanie LegrandINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Geoffroy DanieauINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Régis BrionINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Sarah MoriceINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Laura RegnierINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Maryne DupuyINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Bénédicte Brounais-Le RoyerINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.ORCID 0000-0002-4556-9853
François LamoureuxINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Benjamin OryINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.ORCID 0000-0002-2622-7356
Françoise RédiniINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Franck VerrecchiaINSERM UMR1238 "Bone Sarcomas and Remodeling of Calcified Tissues", Nantes University, 44035 Nantes, France.
Inserm · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Osteosarcoma (OS) is the most common malignant bone tumor in children and teenagers. In many cases, such as poor response to treatment or the presence of metastases at diagnosis, the survival rate of patients remains very low. Although in the literature, more and more studies are emerging on the role of Ubiquitin-Specific Proteases (USPs) in the development of many cancers, few data exist regarding OS. In this context, RNA-sequencing analysis of OS cells and mesenchymal stem cells differentiated or not differentiated into osteoblasts reveals increased expression of four USPs in OS tumor cells: USP6, USP27x, USP41 and USP43. Tissue microarray analysis of patient biopsies demonstrates the nucleic and/or cytoplasmic expression of these four USPs at the protein level. Interestingly, Kaplan-Meyer analysis shows that the expression of two USPs, USP6 and USP41, is correlated with patient survival. In vivo experiments using a preclinical OS model, finally demonstrate that PR619, a USP inhibitor able to enhance protein ubiquitination in OS cell lines, reduces primary OS tumor growth and the development of lung metastases. In this context, in vitro experiments show that PR619 decreases the viability of OS cells, mainly by inducing a caspase3/7-dependent cell apoptosis. Overall, these results demonstrate the relevance of targeting USPs in OS.

Indexed as

AnimalsApoptosisBone NeoplasmsCell MovementCell ProliferationFemaleGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHumansLung NeoplasmsMiceOsteosarcomaPrognosisProtease InhibitorsTumor Cells, CulturedUbiquitin-Specific ProteasesProtease InhibitorsUbiquitin-Specific ProteasesUbiquitin ThiolesteraseUSP27X protein, humanUSP41 protein, humanUSP6 protein, humanOsteosarcomaPR619Ubiquitin Specific Proteases

Identifiers

PMID34571917
PMCPMC8464711
OpenAlexW3197294186

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.