Evidence map›Paper›PMID 20473941›Full record

ArticleInternational journal of cancer2011

A genomic strategy for the functional validation of colorectal cancer genes identifies potential therapeutic targets.

Marian Grade, Amanda B Hummon, Jordi Camps, Georg Emons, Melanie Spitzner, Jochen Gaedcke, Patrick Hoermann, Reinhard Ebner, Heinz Becker, Michael J Difilippantonio and 4 more

Abstract readValidation Study
In one paragraph

Article in International journal of cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
–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

34 citing papers in PubMed.

  1. Article
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  3. Article
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  5. Metabolic synthetic lethality by targeting NOP56 and mTOR in KRAS-mutant lung cancer.Journal of experimental & clinical cancer research : CR · 2022
    Article
  6. [Effect of piRNA NU13 in regulating biological behaviors of human Wilms tumor cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2021
    Article
  7. Article
  8. Article
  9. HMGA1 Promotes Hepatic Metastasis of Colorectal Cancer by Inducing Expression of Glucose Transporter 3 (GLUT3).Medical science monitor : international medical journal of experimental and clinical research · 2020
    Article
  10. Article
  11. Article
  12. Article
  13. A Novel Mechanism Driving Poor-Prognosis Prostate Cancer: Overexpression of the DNA Repair Gene, Ribonucleotide Reductase Small Subunit M2 (RRM2).Clinical cancer research : an official journal of the American Association for Cancer Research · 2019
    Article
  14. Article
  15. Article
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  18. Article
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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

14 authors.

Marian GradeDepartment of General and Visceral Surgery, University Medicine Göttingen, Georg-August-University, Göttingen, Germany.
Amanda B Hummon
Jordi Camps
Georg Emons
Melanie Spitzner
Jochen Gaedcke
Patrick Hoermann
Reinhard Ebner
Heinz Becker
Michael J Difilippantonio
B Michael Ghadimi
Tim Beissbarth
Natasha J Caplen
Thomas Ried

Funding

Identification and functional characterization of colorectal cancer genesZIABC010833 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RIED, THOMAS · 2009 to 2022
$12.1M
Prediction of Therapy Response in Colorectal CancerZIABC010837 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RIED, THOMAS · 2009 to 2022
$8.9M
Consequences of Genomic Instability and Aneuploidy on the Colorectal Cancer TranZIABC010835 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RIED, THOMAS · 2009 to 2016
$6.8M
The Induction of Gene-specific RNAi Against Cancer-associated GenesZIABC010613 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI CAPLEN, NATASHA · 2009 to 2015
$2.4M
Cancer GenomicsZIABC010836 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RIED, THOMAS · 2009 to 2011
$1.8M
Cancer proteomicsZ01BC010836 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI RIED, THOMAS · 2007 to 2008
$1.1M
Intramural NIH HHS Z01 BC010836Intramural NIH HHS Z99 CA999999
6 · The paper itself

Abstract

Genes that are highly overexpressed in tumor cells can be required for tumor cell survival and have the potential to be selective therapeutic targets. In an attempt to identify such targets, we combined a functional genomics and a systems biology approach to assess the consequences of RNAi-mediated silencing of overexpressed genes that were selected from 140 gene expression profiles from colorectal cancers (CRCs) and matched normal mucosa. In order to identify credible models for in-depth functional analysis, we first confirmed the overexpression of these genes in 25 different CRC cell lines. We then identified five candidate genes that profoundly reduced the viability of CRC cell lines when silenced with either siRNAs or short-hairpin RNAs (shRNAs), i.e., HMGA1, TACSTD2, RRM2, RPS2 and NOL5A. These genes were further studied by systematic analysis of comprehensive gene expression profiles generated following siRNA-mediated silencing. Exploration of these RNAi-specific gene expression signatures allowed the identification of the functional space in which the five genes operate and showed enrichment for cancer-specific signaling pathways, some known to be involved in CRC. By comparing the expression of the RNAi signature genes with their respective expression levels in an independent set of primary rectal carcinomas, we could recapitulate these defined RNAi signatures, therefore, establishing the biological relevance of our observations. This strategy identified the signaling pathways that are affected by the prominent oncogenes HMGA1 and TACSTD2, established a yet unknown link between RRM2 and PLK1 and identified RPS2 and NOL5A as promising potential therapeutic targets in CRC.

Indexed as

GenomicsCell Line, TumorColorectal NeoplasmsGene Expression ProfilingGene SilencingHumansImmunohistochemistryRNA Interference

Identifiers

PMID20473941
PMCPMC3008507

What OpenQuestion holds

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LicenceTDM
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 OpenQuestion graph.