Evidence map›Paper›PMID 29731168›Full record

ArticleCell2018

Promoter of lncRNA Gene PVT1 Is a Tumor-Suppressor DNA Boundary Element.

Seung Woo Cho, Jin Xu, Ruping Sun, Maxwell R Mumbach, Ava C Carter, Y Grace Chen, Kathryn E Yost, Jeewon Kim, Jing He, Stephanie A Nevins and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 314 papers.

0numbers the graph read from it
0cells of the map it votes in
314citing papers in PubMed
20.3field-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

314 citing papers in PubMed, 479 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 2 countries.

Seung Woo ChoCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Jin XuCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Ruping SunDepartments of Medicine and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Maxwell R MumbachCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Ava C CarterCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Y Grace ChenCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Kathryn E YostCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Jeewon KimStanford Cancer Institute, Stanford, CA 94305, USA.
Jing HeCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Stephanie A NevinsCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA.
Suet-Feung ChinDepartment of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
Carlos CaldasDepartment of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Breast Cancer Program, CRUK Cambridge Cancer Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK.
S John LiuDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Max A HorlbeckDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Daniel A LimDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; San Francisco Veterans Affairs Medical Center, San Francisco, San Francisco, CA 94121, USA.
Jonathan S WeissmanDepartment of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143, USA; California Institute for Quantitative Biomedical Research, University of California, San Francisco, San Francisco, CA 94143, USA.
Christina CurtisDepartments of Medicine and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford, CA 94305, USA.
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA 94305, USA. Electronic address: howchang@stanford.edu.
Stanford University · USUniversity of California, San Francisco · USCambridge University Hospitals NHS Foundation Trust · GBCancer Research UK Cambridge Center · GBNeurological Surgery · USQB3 · USStanford Cancer Institute

Funding

INSTITUTIONAL TRAINING GRANT IN GENOME SCIENCET32HG000044 · NHGRI · STANFORD UNIVERSITY · PI MICHAEL P. SNYDER · 1995 to 2026
$32.2M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Special EquipmentP50HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2014 to 2018
$15.2M
LncRNA mechanisms in cancerR35CA209919 · NCI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2016 to 2022
$6.4M
Bay Area Cancer Target Discovery and Development NetworkU01CA168370 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCCORMICK, FRANK PATRICK, MCMANUS, MICHAEL T · 2012 to 2016
$3.9M
Harnessing CRISPR for Targeted and Inducible Epigenomic ReprogrammingR01DA036858 · NIDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, WENDELL A, QI, LEI STANLEY · 2013 to 2017
$2.9M
Long noncoding RNA regulation of neural stem cellsR01NS091544 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, DANIEL A · 2016 to 2020
$1.7M
High Throughput DNA Sequencer UpgradeS10OD018220 · OD · STANFORD UNIVERSITY · PI COLLER, JOHN · 2014 to 2014
$596k
Functional long noncoding RNAs in human gliomaR21NS101395 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LIM, DANIEL A · 2017 to 2018
$436k
Cancer Research UK 16942Howard Hughes Medical InstituteNCI NIH HHS R35 CA209919NCI NIH HHS U01 CA168370NHGRI NIH HHS P50 HG007735NHGRI NIH HHS T32 HG000044NIDA NIH HHS R01 DA036858NIGMS NIH HHS T32 GM007618NIH HHS S10 OD018220NINDS NIH HHS R01 NS091544NINDS NIH HHS R21 NS101395
6 · The paper itself

Abstract

Noncoding mutations in cancer genomes are frequent but challenging to interpret. PVT1 encodes an oncogenic lncRNA, but recurrent translocations and deletions in human cancers suggest alternative mechanisms. Here, we show that the PVT1 promoter has a tumor-suppressor function that is independent of PVT1 lncRNA. CRISPR interference of PVT1 promoter enhances breast cancer cell competition and growth in vivo. The promoters of the PVT1 and the MYC oncogenes, located 55 kb apart on chromosome 8q24, compete for engagement with four intragenic enhancers in the PVT1 locus, thereby allowing the PVT1 promoter to regulate pause release of MYC transcription. PVT1 undergoes developmentally regulated monoallelic expression, and the PVT1 promoter inhibits MYC expression only from the same chromosome via promoter competition. Cancer genome sequencing identifies recurrent mutations encompassing the human PVT1 promoter, and genome editing verified that PVT1 promoter mutation promotes cancer cell growth. These results highlight regulatory sequences of lncRNA genes as potential disease-associated DNA elements.

Indexed as

Gene Expression Regulation, NeoplasticGenes, mycAnimalsBreast NeoplasmsCarcinogenesisCell Line, TumorCell ProliferationCell Transformation, NeoplasticChromatinCRISPR-Cas SystemsDNA, NeoplasmEnhancer Elements, GeneticFemaleGene Expression ProfilingHumansMiceChromatinDNA, NeoplasmPVT1 long-non-coding RNA, humanRNA, Long NoncodingCRISPRienhancerlncRNAMYCpromoterPVT1topological domainstranscriptional regulationtumor suppressor

Identifiers

PMID29731168
PMCPMC5984165
OpenAlexW2800290862

What OpenQuestion holds

Textmetadata
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.