Evidence map›Paper›PMID 24726458›Full record

ArticleMolecular oncology2014

Identification of novel non-coding RNA-based negative feedback regulating the expression of the oncogenic transcription factor GLI1.

Victoria E Villegas, Mohammed Ferdous-Ur Rahman, Maite G Fernandez-Barrena, Yumei Diao, Eleni Liapi, Enikö Sonkoly, Mona Ståhle, Andor Pivarcsi, Laura Annaratone, Anna Sapino and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.2field-weighted citation impact, top 22% 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

18 citing papers in PubMed, 25 citations in OpenAlex.

  1. Mechanistic study of antisense long non-coding RNAExploration of targeted anti-tumor therapy · 2026
    Article
  2. Natural antisense transcript ofGenes & development · 2021
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Neighboring gene regulation by antisense long non-coding RNAs.International journal of molecular sciences · 2015
    Review
  17. Article
  18. 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

17 authors at 5 institutions in 4 countries.

Victoria E VillegasDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden; Faculty of Natural Sciences and Mathematics & Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá, Colombia.
Mohammed Ferdous-Ur RahmanDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Maite G Fernandez-BarrenaSchulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN, USA.
Yumei DiaoDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Eleni LiapiDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Enikö SonkolyUnit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Solna, Sweden.
Mona StåhleUnit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Solna, Sweden.
Andor PivarcsiUnit of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Solna, Sweden.
Laura AnnaratoneDepartment of Medical Sciences, University of Turin, Turin, Italy.
Anna SapinoDepartment of Medical Sciences, University of Turin, Turin, Italy.
Sandra Ramírez ClavijoFaculty of Natural Sciences and Mathematics & Doctoral Program in Biomedical Sciences, Universidad del Rosario, Bogotá, Colombia.
Thomas R BürglinDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Takashi ShimokawaDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Saraswathi RamachandranDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden.
Philipp KapranovSt. Laurent Institute, One Kendall Square, Cambridge, MA, USA.
Martin E Fernandez-ZapicoSchulze Center for Novel Therapeutics, Mayo Clinic, Rochester, MN, USA.
Peter G ZaphiropoulosDepartment of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. Electronic address: peter.zaphiropoulos@ki.se.
Karolinska Institutet · SEMayo Clinic · USUniversidad del Rosario · COUniversity of Turin · ITSt. Laurent Institute · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
PILOT AND FEASIBILTY PROGRAMP30DK084567 · NIDDK · MAYO CLINIC ROCHESTER · PI GREGORY J. GORES · 2009 to 2026
$22.2M
Regulation of the Tumor Microenvironment in Hepatocellular CarcinomaR01CA165076 · NCI · MAYO CLINIC ROCHESTER · PI FERNANDEZ-ZAPICO, MARTIN ERNESTO, ROBERTS, LEWIS R · 2012 to 2016
$2.0M
NCI NIH HHS P30 CA015083NCI NIH HHS R01 CA165076NIDDK NIH HHS P30 DK084567
6 · The paper itself

Abstract

Non-coding RNAs are a complex class of nucleic acids, with growing evidence supporting regulatory roles in gene expression. Here we identify a non-coding RNA located head-to-head with the gene encoding the Glioma-associated oncogene 1 (GLI1), a transcriptional effector of multiple cancer-associated signaling pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated GLI1 and increased cellular proliferation and tumor growth in a xenograft model system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1 transcription factor. Activation of TGFβ and Hedgehog signaling, two known regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the interplay between GLI1 and GLI1AS indicates that the non-coding RNA elicits a local alteration of chromatin structure by increasing the silencing mark H3K27me3 and decreasing the recruitment of RNA polymerase II to this locus. Taken together, the data demonstrate the existence of a novel non-coding RNA-based negative feedback loop controlling GLI1 levels, thus expanding the repertoire of mechanisms regulating the expression of this oncogenic transcription factor.

Indexed as

Gene Expression Regulation, NeoplasticCell Line, TumorChromatinHedgehog ProteinsHumansNeoplasmsOncogene ProteinsRNA Polymerase IIRNA, UntranslatedSignal TransductionTrans-ActivatorsTranscriptional ActivationTransforming Growth Factor betaZinc Finger Protein GLI1ChromatinHedgehog ProteinsOncogene ProteinsRNA Polymerase IIRNA, UntranslatedTrans-ActivatorsTransforming Growth Factor betaZinc Finger Protein GLI1CancerChromatinGene expressionGLI1Non-coding RNATranscription

Identifiers

PMID24726458
PMCPMC4082767
OpenAlexW2064679642

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.