Evidence map›Paper›PMID 32087767›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

Downregulation of the Arg/N-degron Pathway Sensitizes Cancer Cells to Chemotherapy In Vivo.

Dominique Leboeuf, Tatiana Abakumova, Tatiana Prikazchikova, Luke Rhym, Daniel G Anderson, Timofei S Zatsepin, Konstantin I Piatkov

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

19 citing papers in PubMed, 32 citations in OpenAlex.

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  16. Signaling Pathways Regulated by UBR Box-Containing E3 Ligases.International journal of molecular sciences · 2021
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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

7 authors at 2 institutions in 2 countries.

Dominique LeboeufSkolkovo Institute of Science and Technology, Moscow, Russia.
Tatiana AbakumovaSkolkovo Institute of Science and Technology, Moscow, Russia.
Tatiana PrikazchikovaSkolkovo Institute of Science and Technology, Moscow, Russia.
Luke RhymDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
Daniel G AndersonDavid H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA; Harvard and MIT Division of Health Science and Technology, Massachusetts Institute of Technology, Cambridge, MA, USA; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA.
Timofei S ZatsepinSkolkovo Institute of Science and Technology, Moscow, Russia.
Konstantin I PiatkovSkolkovo Institute of Science and Technology, Moscow, Russia. Electronic address: k.piatkov@skoltech.ru.
Skolkovo Institute of Science and Technology · RUMassachusetts Institute of Technology · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Jacqueline A. Lees · 1985 to 2026
$93.9M
NCI NIH HHS P30 CA014051
6 · The paper itself

Abstract

The N-degron pathway is an emerging target for anti-tumor therapies, because of its capacity to positively regulate many hallmarks of cancer, including angiogenesis, cell proliferation, motility, and survival. Thus, inhibition of the N-degron pathway offers the potential to be a highly effective anti-cancer treatment. With the use of a small interfering RNA (siRNA)-mediated approach for selective downregulation of the four Arg/N-degron-dependent ubiquitin ligases, UBR1, UBR2, UBR4, and UBR5, we demonstrated decreased cell migration and proliferation and increased spontaneous apoptosis in cancer cells. Chronic treatment with lipid nanoparticles (LNPs) loaded with siRNA in mice efficiently downregulates the expression of UBR-ubiquitin ligases in the liver without any significant toxic effects but engages the immune system and causes inflammation. However, when used in a lower dose, in combination with a chemotherapeutic drug, downregulation of the Arg/N-degron pathway E3 ligases successfully reduced tumor load by decreasing proliferation and increasing apoptosis in a mouse model of hepatocellular carcinoma, while avoiding the inflammatory response. Our study demonstrates that UBR-ubiquitin ligases of the Arg/N-degron pathway are promising targets for the development of improved therapies for many cancer types.

Indexed as

Down-RegulationAnimalsCalmodulin-Binding ProteinsCarcinoma, HepatocellularCell Line, TumorCell MovementCell ProliferationCell SurvivalDoxorubicinDrug SynergismGene Expression Regulation, NeoplasticLiposomesLiver NeoplasmsMiceNanoparticlesRNA, Small InterferingCalmodulin-Binding ProteinsDoxorubicinLipid NanoparticlesLiposomesRNA, Small InterferingUbiquitin-Protein LigasesUBR2 protein, mouseUbr4 protein, mouseUBR5 protein, mouseapoptosischemotherapyhepatocellular carcinomaN-degron pathwayUBR1UBR2UBR4UBR5UBR-ubiquitin ligases

Identifiers

PMID32087767
PMCPMC7132617
OpenAlexW3001039158

What OpenQuestion holds

Textmetadata
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.