Evidence map›Paper›PMID 29980981›Full record

ArticleStem cell reviews and reports2018

Analysis of the Paternally-Imprinted DLK1-MEG3 and IGF2-H19 Tandem Gene Loci in NT2 Embryonal Carcinoma Cells Identifies DLK1 as a Potential Therapeutic Target.

Zachariah Payne Sellers, Gabriela Schneider, Magdalena Maj, Mariusz Z Ratajczak

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Article in Stem cell reviews and reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.7field-weighted citation impact, top 24% 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

5 citing papers in PubMed, 8 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

4 authors at 2 institutions in 2 countries.

Zachariah Payne SellersStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA.
Gabriela SchneiderStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA.
Magdalena MajStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA.
Mariusz Z RatajczakStem Cell Institute at James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Louisville, KY, 40202, USA. mzrata01@louisville.edu.
James Graham Brown Foundation · USMedical University of Warsaw · PL

Funding

Novel mechanisms involving complement cascade in stem cell traffickingR01DK074720 · NIDDK · UNIVERSITY OF LOUISVILLE · PI RATAJCZAK, MARIUSZ Z · 2007 to 2020
$4.1M
BIOACTIVE LIPIDS IN STEM CELL HOMING AND MOBILIZATIONR01HL112788 · NHLBI · UNIVERSITY OF LOUISVILLE · PI RATAJCZAK, MARIUSZ Z · 2013 to 2016
$1.5M
NHLBI NIH HHS R01 HL112788NIDDK NIH HHS 2R01 DK074720
6 · The paper itself

Abstract

The paternally-imprinted genes insulin-like growth factor 2 (IGF2), H19, delta-like homologue 1 (DLK1), and maternally-expressed gene 3 (MEG3) are expressed from the tandem gene loci IGF2-H19 and DLK1-MEG3, which play crucial roles in initiating embryogenesis and development. The erasure of imprinting (EOI) at differentially methylated regions (DMRs) which regulate the expression of these genes maintains the developmental quiescence of primordial germ cells (PGCs) migrating through the embryo proper during embryogenesis and prevents them from forming teratomas. To address the potential involvement of the IGF2-H19 and DLK1-MEG3 loci in the pathogenesis of embryonal carcinoma (EC), we investigated their genomic imprinting at DMRs in the human PGC-derived EC cell line NTera-2 (NT2). We observed EOI at the IGF2-H19 locus and, somewhat to our surprise, a loss of imprinting (LOI) at the DLK1-MEG3 locus. As a result, NT2 cells express imprinted gene ratios from these loci such that there are i) low levels of the proliferation-promoting IGF2 relative to ii) high levels of the proliferation-inhibiting long noncoding RNA (lncRNA) H19 and iii) high levels of proliferation-promoting DLK1 relative to iv) low levels of the proliferation-inhibiting lncRNA MEG3. Consistent with this pattern of expression, the knockdown of DLK1 mRNA by shRNA resulted in decreased in vitro cell proliferation and in vivo tumor growth as well as decreased in vivo organ seeding by NT2 cells. Furthermore, treatment of NT2 cells with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-azaD) inhibited their proliferation. This inhibition was accompanied by changes in expression of both tandem gene sets: a decrease in the expression of DLK1 and upregulation of the proliferation-inhibiting lncRNA MEG3, and at the same time upregulation of IGF2 and downregulation of the lncRNA H19. These results suggest that the DLK1-MEG3 locus, and not the IGF2-H19 locus, drives the tumorigenicity of NT2 cells. Based on these results, we identified DLK1 as a novel treatment target for EC that could be downregulated by 5-azaD.

Indexed as

Carcinoma, EmbryonalGenetic LociGenomic ImprintingInsulin-Like Growth Factor IIIntercellular Signaling Peptides and ProteinsMembrane ProteinsNeoplasm ProteinsRNA, Long NoncodingRNA, NeoplasmCalcium-Binding ProteinsCell Line, TumorHumansCalcium-Binding ProteinsDLK1 protein, humanH19 long non-coding RNAIGF2 protein, humanInsulin-Like Growth Factor IIIntercellular Signaling Peptides and ProteinsMEG3 non-coding RNA, humanMembrane ProteinsNeoplasm ProteinsRNA, Long NoncodingRNA, Neoplasm5-azaDDLK1Embryonal carcinomaImprintingMetastasisPluripotencyPrimordial germ cellsProliferationTeratocarcinoma

Identifiers

PMID29980981
OpenAlexW2860543013

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.