Evidence map›Paper›PMID 36811655›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2023

Histone H3K9 methyltransferase SETDB1 overexpression correlates with pediatric high-grade gliomas progression and prognosis.

Alexia Klonou, Penelope Korkolopoulou, Angeliki-Ioanna Giannopoulou, Dimitrios S Kanakoglou, Andromachi Pampalou, Antonios N Gargalionis, Panagiotis Sarantis, Andreas Mitsios, Spyros Sgouros, Athanasios G Papavassiliou and 1 more

Abstract read
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In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
2.6field-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

7 citing papers in PubMed, 9 citations in OpenAlex.

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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

11 authors at 1 institution in 1 country.

Alexia KlonouDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg 16, 11527, Athens, Greece.
Penelope Korkolopoulou *First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Angeliki-Ioanna Giannopoulou *Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg 16, 11527, Athens, Greece.
Dimitrios S KanakoglouFirst Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Andromachi PampalouFirst Department of Pathology, Medical School, National and Kapodistrian University of Athens, 11527, Athens, Greece.
Antonios N GargalionisDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg 16, 11527, Athens, Greece.
Panagiotis SarantisDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg 16, 11527, Athens, Greece.
Andreas MitsiosDepartment of Pediatric Neurosurgery, IASO Children's Hospital, National and Kapodistrian University of Athens, 15123, Athens, Greece.
Spyros SgourosDepartment of Pediatric Neurosurgery, IASO Children's Hospital, National and Kapodistrian University of Athens, 15123, Athens, Greece.
Athanasios G PapavassiliouDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg 16, 11527, Athens, Greece. papavas@med.uoa.gr.
Christina PiperiDepartment of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias Street - Bldg 16, 11527, Athens, Greece. cpiperi@med.uoa.gr.ORCID 0000-0002-2701-0618
National and Kapodistrian University of Athens · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Pediatric high-grade gliomas (pHGGs) are heterogeneous, diffuse, and highly infiltrative tumors with dismal prognosis. Aberrant post-translational histone modifications with elevated histone 3 lysine trimethylation (H3K9me3) have been recently implicated in pHGGs' pathology, conferring to tumor heterogeneity. The present study investigates the potential involvement of H3K9me3 methyltransferase SETDB1 in the cellular function, progression, and clinical significance of pHGG. The bioinformatic analysis detected SETDB1 enrichment in pediatric gliomas compared to the normal brain, as well as positive and negative correlations with a proneural and mesenchymal signature, respectively. In our cohort of pHGGs, SETDB1 expression was significantly increased compared to pLGG and normal brain tissue and correlated with p53 expression, as well as reduced patients' survival. In accordance, H3K9me3 levels were also elevated in pHGG compared to the normal brain and were associated with worse patient survival. Gene silencing of SETDB1 in two patient-derived pHGG cell lines showed a significant reduction in cell viability followed by reduced cell proliferation and increased apoptosis. SETDB1 silencing further reduced cell migration of pHGG cells and the expression of the mesenchymal markers N-cadherin and vimentin. mRNA analysis of epithelial-mesenchymal transition (EMT) markers upon SETDB1 silencing showed a reduction in SNAI1 levels and downregulation of CDH2 along with the EMT regulator gene MARCKS. In addition, SETDB1 silencing significantly increased the bivalent tumor suppressor gene SLC17A7 mRNA levels in both cell lines, indicating its implication in the oncogenic process.Altogether, our findings demonstrate a predominant oncogenic role of SETDB1 in pHGG which along with elevated H3K9me3 levels correlate significantly to tumor progression and inferior patients' survival. There is evidence that targeting SETDB1 may effectively inhibit pHGG progression, providing a novel insight into the therapeutic strategies for pediatric gliomas. KEY MESSAGES: SETDB1 gene expression is enriched in pHGG compared to normal brain. SETDB1 expression is increased in pHGG tissues and associates with reduced patients' survival. Gene silencing of SETDB1 reduces cell viability and migration. SETDB1 silencing affects mesenchymal markers expression. SETDB1 silencing upregulates SLC17A7 levels. SETDB1 has an oncogenic role in pHGG.

Indexed as

GliomaHistonesCell LineChildHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHumansRNA, MessengerHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHistonesRNA, MessengerSETDB1 protein, humanCDH2H3K9me3MARCKSMBD1N-cadherinp53Pediatric high-grade gliomasSETDB1SLC17A7SNAI1Vimentin

Identifiers

PMID36811655
OpenAlexW4321499050

What Socratic 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 Socratic graph.