Evidence map›Paper›PMID 27378691›Full record

ArticleHuman molecular genetics2016

Long-range regulators of the lncRNA HOTAIR enhance its prognostic potential in breast cancer.

Michael J G Milevskiy, Fares Al-Ejeh, Jodi M Saunus, Korinne S Northwood, Peter J Bailey, Joshua A Betts, Amy E McCart Reed, Kenneth P Nephew, Andrew Stone, Julia M W Gee and 8 more

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

Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 6% 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

46 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

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  10. Epigenetics, cryptorchidism, and infertility.Basic and clinical andrology · 2023
    Article
  11. The lncRNA HOTAIR: a pleiotropic regulator of epithelial cell plasticity.Journal of experimental & clinical cancer research : CR · 2023
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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

18 authors at 6 institutions in 3 countries.

Michael J G MilevskiySchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Fares Al-EjehQIMR Berghofer Medical Research Institute, Brisbane, Australia.
Jodi M SaunusThe University of Queensland, UQ Centre for Clinical Research, Herston, Australia.
Korinne S NorthwoodSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Peter J BaileySchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Joshua A BettsSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Amy E McCart ReedThe University of Queensland, UQ Centre for Clinical Research, Herston, Australia.
Kenneth P NephewIndiana University, School of Medicine, Bloomington, IN, USA.
Andrew StoneEpigenetics Research Laboratory, Division of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Julia M W GeeSchool of Pharmacy & Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
Dennis H DowhanInstitute for Molecular Bioscience, The University of Queensland, Brisbane, Australia.
Eloise DraySchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Annette M ShewanSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Juliet D FrenchSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Stacey L EdwardsSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia.
Susan J ClarkEpigenetics Research Laboratory, Division of Genomics and Epigenetics, Garvan Institute of Medical Research, Sydney, NSW, Australia.
Sunil R LakhaniThe University of Queensland, UQ Centre for Clinical Research, Herston, Australia.
Melissa A BrownSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Australia melissa.brown@uq.edu.au.
University of Queensland · AUQIMR Berghofer Medical Research Institute · AUGarvan Institute of Medical Research · AUCardiff University · GBIndiana University Bloomington · USQueensland University of Technology · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Predicting response to endocrine therapy and survival in oestrogen receptor positive breast cancer is a significant clinical challenge and novel prognostic biomarkers are needed. Long-range regulators of gene expression are emerging as promising biomarkers and therapeutic targets for human diseases, so we have explored the potential of distal enhancer elements of non-coding RNAs in the prognostication of breast cancer survival. HOTAIR is a long non-coding RNA that is overexpressed, promotes metastasis and is predictive of decreased survival. Here, we describe a long-range transcriptional enhancer of the HOTAIR gene that binds several hormone receptors and associated transcription factors, interacts with the HOTAIR promoter and augments transcription. This enhancer is dependent on Forkhead-Box transcription factors and functionally interacts with a novel alternate HOTAIR promoter. HOTAIR expression is negatively regulated by oestrogen, positively regulated by FOXA1 and FOXM1, and is inversely correlated with oestrogen receptor and directly correlated with FOXM1 in breast tumours. The combination of HOTAIR and FOXM1 enables greater discrimination of endocrine therapy responders and non-responders in patients with oestrogen receptor positive breast cancer. Consistent with this, HOTAIR expression is increased in cell-line models of endocrine resistance. Analysis of breast cancer gene expression data indicates that HOTAIR is co-expressed with FOXA1 and FOXM1 in HER2-enriched tumours, and these factors enhance the prognostic power of HOTAIR in aggressive HER2+ breast tumours. Our study elucidates the transcriptional regulation of HOTAIR, identifies HOTAIR and its regulators as novel biomarkers of patient response to endocrine therapy and corroborates the importance of transcriptional enhancers in cancer.

Indexed as

Gene Expression Regulation, NeoplasticTranscription, GeneticBiomarkers, TumorBreast NeoplasmsFemaleForkhead Box Protein M1Hepatocyte Nuclear Factor 3-alphaHumansMCF-7 CellsNeoplasm ProteinsRNA, Long NoncodingRNA, NeoplasmBiomarkers, TumorForkhead Box Protein M1FOXA1 protein, humanFOXM1 protein, humanHepatocyte Nuclear Factor 3-alphaHOTAIR long untranslated RNA, humanNeoplasm ProteinsRNA, Long NoncodingRNA, Neoplasm

Identifiers

PMID27378691
PMCPMC5179926
OpenAlexW2466943387

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.