Evidence map›Paper›PMID 25817443›Full record

ArticleMolecular oncology2015

Instability of a dinucleotide repeat in the 3'-untranslated region (UTR) of the microsomal prostaglandin E synthase-1 (mPGES-1) gene in microsatellite instability-high (MSI-H) colorectal carcinoma.

Durga Prasad Cherukuri, Joshua L Deignan, Kingshuk Das, Wayne W Grody, Harvey Herschman

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

Article in Molecular oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 42% 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

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
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.

Durga Prasad CherukuriDepartment of Pharmacology and UCLA Intercampus Medical Genetics Training Program, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Joshua L DeignanDepartments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Kingshuk DasDepartments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Wayne W GrodyDepartments of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Harvey HerschmanDepartment of Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. Electronic address: hherschman@mednet.ucla.edu.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Transductionally Redirected /Transcriptionally RestricteP50CA086306 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HERSCHMAN, HARVEY R. · 2000 to 2014
$29.0M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
NCI NIH HHS P30 CA016042NCI NIH HHS P50 CA086306NCI NIH HHS P50CA86306NIDDK NIH HHS P30 DK041301
6 · The paper itself

Abstract

DNA mismatch-repair gene mutations, with consequent loss of functional protein expression, result in microsatellite instability (MSI). Microsatellite sequences are found in coding regions and in regulatory regions of genes (i.e., 5'-UTRs and 3'-UTRs). In addition to being a surrogate marker of defective mismatch repair, deletion or insertion microsatellite sequences can dysregulate gene expression in MSI-H (microsatellite instability-high) tumors. The microsomal prostaglandin E synthase-1 (mPGES-1) gene product, mPGES-1, participates in prostaglandin E2 (PGE2) production. Moreover, mPGES-1 is often overexpressed in human colorectal tumors, and is thought to contribute to progression of these tumors. Here we identified a dinucleotide repeat, (GT)24, in the mPGES-1 gene 3' untranslated region (3'-UTR), and analyzed its mutation frequencies in MSI-H and microsatellite stable (MSS) tumors. The (GT)24 repeat exhibited instability in all MSI-H tumors examined (14), but not in any of the MSS tumors (13). In most cases, (GT)24 repeat instability resulted in insertion of additional GT units. We also determined mPGES-1 mRNA levels in MSI-H and MSS colorectal cancer cell lines. Three of four previously designated "MSI-H" cell lines showed higher mPGES-1 mRNA levels compared to MSS cell lines; correlations between elevated mPGES-1 mRNA levels and microsatellite (GT)24 repeat characteristics are present for all six cell lines. Our results demonstrate that mPGES-1 is a target gene of defective mismatch repair in human colorectal cancer, with functional consequence.

Indexed as

3' Untranslated RegionsDinucleotide RepeatsMicrosatellite InstabilityCell Line, TumorColorectal NeoplasmsHumansIntramolecular OxidoreductasesProstaglandin-E SynthasesRNA, Messenger3' Untranslated RegionsIntramolecular OxidoreductasesProstaglandin-E SynthasesPTGES protein, humanRNA, MessengerColorectal cancerDinucleotide repeatMicrosatellite instabilitymPGES-1

Identifiers

PMID25817443
PMCPMC4523444
OpenAlexW2095668333

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.