Evidence map›Paper›PMID 24149370›Full record

ArticleEpigenetics2014

Epigenetic regulation of miR-21 in colorectal cancer: ITGB4 as a novel miR-21 target and a three-gene network (miR-21-ITGΒ4-PDCD4) as predictor of metastatic tumor potential.

Angelo Ferraro, Christos K Kontos, Themis Boni, Ioannis Bantounas, Dimitra Siakouli, Vivian Kosmidou, Margarita Vlassi, Yannis Spyridakis, Iraklis Tsipras, George Zografos and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

65 citing papers in PubMed, 106 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Review
  5. Evidence for a TMAO-HULC-miRNA regulatory axis in colorectal cancer cells.International journal of molecular and cellular medicine · 2025
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  15. High Expression of a tRNABiomedicines · 2022
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  16. METTL14-mediated NCell communication and signaling : CCS · 2022
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  17. Review
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  20. Review

5 more citing papers are in PubMed but not listed here.

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 3 institutions in 2 countries.

Angelo FerraroLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Christos K KontosLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Themis BoniLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Ioannis BantounasLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Dimitra SiakouliLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Vivian KosmidouLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Margarita VlassiLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Yannis Spyridakis3rd Department of Surgery; General Hospital of Athens G. Gennimatas; Athens, Greece.
Iraklis Tsipras3rd Department of Surgery; General Hospital of Athens G. Gennimatas; Athens, Greece.
George Zografos3rd Department of Surgery; General Hospital of Athens G. Gennimatas; Athens, Greece.
Alexander PintzasLaboratory of Signal Mediated Gene Expression; Institute of Biology, Medicinal Chemistry and Biotechnology; National Hellenic Research Foundation; Athens, Greece.
Expression Génétique Microbienne · FRGeneral Hospital of Athens G. Genimatas · GRNational Hellenic Research Foundation · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Previous studies have uncovered several transcription factors that determine biological alterations in tumor cells to execute the invasion-metastasis cascade, including the epithelial-mesenchymal transition (EMT). We sought to investigate the role of miR-21 in colorectal cancer regulation. For this purpose, miR-21 expression was quantified in a panel of colorectal cancer cell lines and clinical specimens. High expression was found in cell lines with EMT properties and in the vast majority of human tumor specimens. We demonstrate in a cell-specific manner the occupancy of MIR-21 gene promoter by AP-1 and ETS1 transcription factors and, for the first time, the pattern of histone posttranslational modifications necessary for miR-21 overexpression. We also show that Integrin-β4 (ITGβ4), exclusively expressed in polarized epithelial cells, is a novel miR-21 target gene and plays a role in the regulation of EMT, since it is remarkably de-repressed after transient miR-21 silencing and downregulated after miR-21 overexpression. miR-21-dependent change of ITGβ4 expression significantly affects cell migration properties of colon cancer cells. Finally, in a subgroup of tumor specimens, ROC curve analysis performed on quantitative PCR data sets for miR-21, ITGβ4, and PDCD4 shows that the combination of high miR-21 with low ITGβ4 and PDCD4 expression is able to predict presence of metastasis. In conclusion, miR-21 is a key player in oncogenic EMT, its overexpression is controlled by the cooperation of genetic and epigenetic alterations, and its levels, along with ITGβ4 and PDCD4 expression, could be exploited as a prognostic tool for CRC metastasis.

Indexed as

Epigenesis, GeneticGene Regulatory NetworksApoptosis Regulatory ProteinsBiomarkers, TumorCell Line, TumorColorectal NeoplasmsEpithelial-Mesenchymal TransitionHistonesHumansIntegrin beta4MicroRNAsNeoplasm MetastasisProtein Processing, Post-TranslationalProto-Oncogene Protein c-ets-1RNA-Binding ProteinsTranscription Factor AP-1Apoptosis Regulatory ProteinsBiomarkers, TumorETS1 protein, humanHistonesIntegrin beta4ITGB4 protein, humanMicroRNAsMIRN21 microRNA, humanPDCD4 protein, humanProto-Oncogene Protein c-ets-1RNA-Binding ProteinsTranscription Factor AP-1epithelial-mesenchymal transition (EMT)histone modificationsITGβ4metastasis markersmiR-21RAS

Identifiers

PMID24149370
PMCPMC3928175
OpenAlexW2090786568

What OpenQuestion 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 OpenQuestion graph.