Evidence map›Paper›PMID 25417700›Full record

ArticleOncogene2015

Tumor hypoxia induces nuclear paraspeckle formation through HIF-2α dependent transcriptional activation of NEAT1 leading to cancer cell survival.

H Choudhry, A Albukhari, M Morotti, S Haider, D Moralli, J Smythies, J Schödel, C M Green, C Camps, F Buffa and 4 more

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

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 149 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 1 pooled it
10.4field-weighted citation impact, top 1% 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

149 citing papers in PubMed, 1 synthesis or guideline pooled it, 310 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
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  11. Article
  12. Rewiring cancer epigenome: lncRNA as modulator of chromatin architecture and neoplastic transformation.Mammalian genome : official journal of the International Mammalian Genome Society · 2025
    Review
  13. Review
  14. Doxorubicin Effects Breast Cancer Proliferation via the NEAT1/miR-410-3p Axis.Asian Pacific journal of cancer prevention : APJCP · 2025
    Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Single-cell analysis reveals that GFAPCell death & disease · 2025
    Article
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 5 countries.

H ChoudhryDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
A AlbukhariDepartment of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
M MorottiWeatherall Institute of Molecular Medicine, Department of Oncology, University of Oxford, Oxford, UK.
S HaiderWeatherall Institute of Molecular Medicine, Department of Oncology, University of Oxford, Oxford, UK.
D MoralliThe Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK.
J SmythiesThe Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington, Oxford, UK.
J SchödelDepartment of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
C M GreenThe Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK.
C CampsThe Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK.
F BuffaOld Road Campus Research Building, University of Oxford, Headington, Oxford, UK.
P RatcliffeThe Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington, Oxford, UK.
J RagoussisThe Wellcome Trust Centre for Human Genetics, University of Oxford, Headington, Oxford, UK.
A L HarrisWeatherall Institute of Molecular Medicine, Department of Oncology, University of Oxford, Oxford, UK.
D R MoleThe Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington, Oxford, UK.
University of Oxford · GBMRC Weatherall Institute of Molecular Medicine · GBCentre for Human Genetics · GBAlexander Fleming Biomedical Sciences Research Center · GRFriedrich-Alexander-Universität Erlangen-Nürnberg · DE

Funding

Cancer Research UK 11359Cancer Research UK 16016Cancer Research UK 18974Wellcome Trust 078333/Z/05/ZWellcome Trust 088182Wellcome Trust 088182/Z/09/ZWellcome Trust WT091857MA
6 · The paper itself

Abstract

Activation of cellular transcriptional responses, mediated by hypoxia-inducible factor (HIF), is common in many types of cancer, and generally confers a poor prognosis. Known to induce many hundreds of protein-coding genes, HIF has also recently been shown to be a key regulator of the non-coding transcriptional response. Here, we show that NEAT1 long non-coding RNA (lncRNA) is a direct transcriptional target of HIF in many breast cancer cell lines and in solid tumors. Unlike previously described lncRNAs, NEAT1 is regulated principally by HIF-2 rather than by HIF-1. NEAT1 is a nuclear lncRNA that is an essential structural component of paraspeckles and the hypoxic induction of NEAT1 induces paraspeckle formation in a manner that is dependent upon both NEAT1 and on HIF-2. Paraspeckles are multifunction nuclear structures that sequester transcriptionally active proteins as well as RNA transcripts that have been subjected to adenosine-to-inosine (A-to-I) editing. We show that the nuclear retention of one such transcript, F11R (also known as junctional adhesion molecule 1, JAM1), in hypoxia is dependent upon the hypoxic increase in NEAT1, thereby conferring a novel mechanism of HIF-dependent gene regulation. Induction of NEAT1 in hypoxia also leads to accelerated cellular proliferation, improved clonogenic survival and reduced apoptosis, all of which are hallmarks of increased tumorigenesis. Furthermore, in patients with breast cancer, high tumor NEAT1 expression correlates with poor survival. Taken together, these results indicate a new role for HIF transcriptional pathways in the regulation of nuclear structure and that this contributes to the pro-tumorigenic hypoxia-phenotype in breast cancer.

Indexed as

Cell HypoxiaTranscriptional ActivationAnimalsApoptosisBasic Helix-Loop-Helix ProteinsBreast NeoplasmsCell Adhesion MoleculesCell ProliferationCell SurvivalEndothelial PAS Domain-Containing Protein 1FemaleHumansMiceReceptors, Cell SurfaceRNA, Long NoncodingBasic Helix-Loop-Helix ProteinsCell Adhesion MoleculesEndothelial PAS Domain-Containing Protein 1F11R protein, humanNEAT1 long non-coding RNA, humanReceptors, Cell SurfaceRNA, Long Noncoding

Identifiers

PMID25417700
PMCPMC4430310
OpenAlexW2087351768

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Registered trials

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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.