Evidence map›Paper›PMID 34815475›Full record

ArticleScientific reports2021

EZH2 presents a therapeutic target for neuroendocrine tumors of the small intestine.

Elham Barazeghi, Per Hellman, Olov Norlén, Gunnar Westin, Peter Stålberg

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

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. Review
  6. Multifaceted modeling of small intestinal neuroendocrine tumors.Endocrine oncology (Bristol, England) · 2024
    Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Metformin and Cancer, an Ambiguanidous Relationship.Pharmaceuticals (Basel, Switzerland) · 2022
    Review
  12. Review
  13. Article
  14. 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

5 authors at 1 institution in 1 country.

Elham BarazeghiDepartment of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, 751 85, Uppsala, Sweden. elham.barazeghi@surgsci.uu.se.
Per HellmanDepartment of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, 751 85, Uppsala, Sweden.
Olov NorlénDepartment of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, 751 85, Uppsala, Sweden.
Gunnar WestinDepartment of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, 751 85, Uppsala, Sweden.
Peter StålbergDepartment of Surgical Sciences, Uppsala University, Uppsala University Hospital, Rudbeck Laboratory, 751 85, Uppsala, Sweden. peter.stalberg@surgsci.uu.se.
Uppsala University Hospital · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Small intestinal neuroendocrine tumors (SI-NETs) are slow-growing tumors that seem genetically quite stable without highly recurrent mutations, but are epigenetically dysregulated. In contrast to the undetectable expression of the enhancer of zeste homolog 2 (EZH2) histone methyltransferase in the enterochromaffin cells of the small intestine, we found high and differential expression of EZH2 in primary SI-NETs and corresponding metastases. Silencing EZH2 in the SI-NET cell line CNDT2.5 reduced cell proliferation and induced apoptosis. Furthermore, EZH2 knockout inhibited tumor progression in a CNDT2.5 SI-NET xenograft mouse model, and treatment of SI-NET cell lines CNDT2.5 and GOT1 with the EZH2-specific inhibitor CPI-1205 decreased cell viability and promoted apoptosis. Moreover, CPI-1205 treatment reduced migration capacity of CNDT2.5 cells. The EZH2 inhibitor GSK126 also repressed proliferation of CNDT2.5 cells. Recently, metformin has received wide attention as a therapeutic option in diverse cancers. In CNDT2.5 and GOT1 cells, metformin suppressed EZH2 expression, and inhibited cell proliferation. Exposure of GOT1 three-dimensional cell spheroids to CPI-1205 or metformin arrested cell proliferation and decreased spheroid size. These novel findings support a possible role of EZH2 as a candidate oncogene in SI-NETs, and suggest that CPI-1205 and metformin should be further evaluated as therapeutic options for patients with SI-NETs.

Indexed as

Gene Expression Regulation, NeoplasticAnimalsApoptosisBiomarkers, TumorCell MovementCell ProliferationDrug Therapy, CombinationEnhancer of Zeste Homolog 2 ProteinEnzyme InhibitorsFemaleHumansHypoglycemic AgentsIndolesIntestinal NeoplasmsIntestine, SmallMetforminBiomarkers, TumorEnhancer of Zeste Homolog 2 ProteinEnzyme InhibitorsEZH2 protein, humanHypoglycemic AgentsIndolesMetforminPiperidines(R)-N-((4-methoxy-6-methyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-1-(1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)ethyl)-1H-indole-3-carboxamide

Identifiers

PMID34815475
PMCPMC8611048
OpenAlexW3217779333

What Socratic holds

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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 Socratic graph.