Evidence map›Paper›PMID 25944909›Full record

ArticleThe Journal of biological chemistry2015

Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC).

Jyoti Srivastava, Chadia L Robertson, Rachel Gredler, Ayesha Siddiq, Devaraja Rajasekaran, Maaged A Akiel, Luni Emdad, Valeria Mas, Nitai D Mukhopadhyay, Paul B Fisher and 1 more

Abstract read
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In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

16 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
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  7. Expression patterns of AEG-1 in the normal brain.Brain structure & function · 2023
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  11. Observational
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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.

Jyoti SrivastavaDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
Chadia L RobertsonDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
Rachel GredlerDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
Ayesha SiddiqDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
Devaraja RajasekaranDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
Maaged A AkielDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
Luni EmdadDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298.
Valeria MasDepartment of Surgery, University of Virginia, Charlottesville, Virginia 22908-0625.
Nitai D MukhopadhyayBiostatistics, Virginia Commonwealth University, Richmond, Virginia 23298.
Paul B FisherDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298; Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298; VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia 23298.
Devanand SarkarDepartments of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, Virginia 23298; Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia 23298; VCU Institute of Molecular Medicine, Virginia Commonwealth University, Richmond, Virginia 23298. Electronic address: dsarkar@vcu.edu.

Funding

Training Grant in Digestive Diseases and Liver DiseasesT32DK007150 · NIDDK · VIRGINIA COMMONWEALTH UNIVERSITY · PI SANYAL, ARUN J · 1986 to 2017
$4.2M
Analysis of a novel regulator of hepatocellular carcinomaR01CA138540 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SARKAR, DEVANAND · 2010 to 2014
$1.6M
AEG-1: Novel Gene Involved in Malignant GliomaR01CA134721 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI FISHER, PAUL B · 2009 to 2013
$1.5M
A novel mediator of obesity associated hepatocellular carcinoma (HCC)R21CA183954 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI SARKAR, DEVANAND · 2014 to 2015
$365k
NCI NIH HHS R01 CA134721NCI NIH HHS R01 CA138540NCI NIH HHS R21 CA183954NIDDK NIH HHS T32 DK007150NIDDK NIH HHS T32DK007150
6 · The paper itself

Abstract

Non-thyroidal illness syndrome (NTIS), characterized by low serum 3,5,3'-triiodothyronine (T3) with normal l-thyroxine (T4) levels, is associated with malignancy. Decreased activity of type I 5'-deiodinase (DIO1), which converts T4 to T3, contributes to NTIS. T3 binds to thyroid hormone receptor, which heterodimerizes with retinoid X receptor (RXR) and regulates transcription of target genes, such as DIO1. NF-κB activation by inflammatory cytokines inhibits DIO1 expression. The oncogene astrocyte elevated gene-1 (AEG-1) inhibits RXR-dependent transcription and activates NF-κB. Here, we interrogated the role of AEG-1 in NTIS in the context of hepatocellular carcinoma (HCC). T3-mediated gene regulation was analyzed in human HCC cells, with overexpression or knockdown of AEG-1, and primary hepatocytes from AEG-1 transgenic (Alb/AEG-1) and AEG-1 knock-out (AEG-1KO) mice. Serum T3 and T4 levels were checked in Alb/AEG-1 mice and human HCC patients. AEG-1 and DIO1 levels in human HCC samples were analyzed by immunohistochemistry. AEG-1 inhibited T3-mediated gene regulation in human HCC cells and mouse hepatocytes. AEG-1 overexpression repressed and AEG-1 knockdown induced DIO1 expression. An inverse correlation was observed between AEG-1 and DIO1 levels in human HCC patients. Low T3 with normal T4 was observed in the sera of HCC patients and Alb/AEG-1 mice. Inhibition of co-activator recruitment to RXR and activation of NF-κB were identified to play a role in AEG-1-mediated down-regulation of DIO1. AEG-1 thus might play a role in NTIS associated with HCC and other cancers.

Indexed as

AnimalsCarcinoma, HepatocellularCell Adhesion MoleculesCell Line, TumorDown-RegulationEuthyroid Sick SyndromesGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticHEK293 CellsHepatocytesHumansIodide PeroxidaseLiver NeoplasmsMembrane GlycoproteinsMembrane ProteinsMiceCell Adhesion MoleculesCrisp1 protein, mouseIodide PeroxidaseMembrane GlycoproteinsMembrane ProteinsMTDH protein, humanNeoplasm ProteinsNF-kappa BRetinoid X ReceptorsRNA-Binding Proteinsselenodeiodinase type 1, mouseTriiodothyronineAEG-1hepatocellular carcinomaliverNF-kappa Bnon-thyroidal illness syndromethyroid hormonetranscriptional coactivator

Identifiers

PMID25944909
PMCPMC4505468

What OpenQuestion holds

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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.