Evidence map›Paper›PMID 27758885›Full record

ArticleCancer research2016

Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation.

Wayne O Miles, Antonio Lembo, Angela Volorio, Elena Brachtel, Bin Tian, Dennis Sgroi, Paolo Provero, Nicholas Dyson

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.6field-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

41 citing papers in PubMed, 64 citations in OpenAlex.

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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

8 authors at 3 institutions in 2 countries.

Wayne O MilesDepartment of Molecular Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. dyson@helix.mgh.harvard.edu wayne.miles@osumc.edu.
Antonio LemboDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Angela VolorioDepartment of Pathology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
Elena BrachtelDepartment of Pathology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
Bin TianDepartment of Microbiology, Biochemistry and Molecular Genetics, Rutgers New Jersey Medical School, Newark, New Jersey.
Dennis SgroiDepartment of Pathology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts.
Paolo ProveroDepartment of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Nicholas DysonDepartment of Molecular Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts. dyson@helix.mgh.harvard.edu wayne.miles@osumc.edu.
Massachusetts General Hospital · USVita-Salute San Raffaele University · ITRutgers, The State University of New Jersey · US

Funding

Regulation of Alternative Cleavage and PolyadenylationR01GM084089 · NIGMS · WISTAR INSTITUTE · PI TIAN, BIN · 2008 to 2023
$6.7M
MUTAGENESIS OF THE PRB POCKET DOMAINR01CA064402 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DYSON, NICHOLAS J · 1994 to 2015
$4.1M
A NOVEL BREAST CANCER BIOMARKERR01CA112021 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SGROI, DENNIS C · 2005 to 2013
$2.6M
Dissection and manipulation of RB functionR01CA163698 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI DYSON, NICHOLAS J · 2012 to 2016
$1.8M
Interplay between transcription and translationK22CA204352 · NCI · OHIO STATE UNIVERSITY · PI MILES, WAYNE · 2016 to 2018
$561k
NCI NIH HHS K22 CA204352NCI NIH HHS R01 CA064402NCI NIH HHS R01 CA112021NCI NIH HHS R01 CA163698NIGMS NIH HHS R01 GM084089
6 · The paper itself

Abstract

Alternative polyadenylation (APA) is a process that changes the posttranscriptional regulation and translation potential of mRNAs via addition or deletion of 3' untranslated region (3' UTR) sequences. To identify posttranscriptional-regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3' UTR regions found that APA-mediated removal of Pumilio regulatory elements (PRE) was unusually common. Breast tumor subtype-specific APA profiling identified triple-negative breast tumors as having the highest levels of APA. To determine the frequency of these events, an independent cohort of triple-negative breast tumors and normal breast tissue was analyzed for APA. APA-mediated shortening of NRAS and c-JUN was seen frequently, and this correlated with changes in the expression of downstream targets. mRNA stability and luciferase assays demonstrated APA-dependent alterations in RNA and protein levels of affected candidate genes. Examination of clinical parameters of these tumors found those with APA of NRAS and c-JUN to be smaller and less proliferative, but more invasive than non-APA tumors. RT-PCR profiling identified elevated levels of polyadenylation factor CSTF3 in tumors with APA. Overexpression of CSTF3 was common in triple-negative breast cancer cell lines, and elevated CSTF3 levels were sufficient to induce APA of NRAS and c-JUN. Our results support the hypothesis that PRE-containing mRNAs are disproportionately affected by APA, primarily due to high sequence similarity in the motifs utilized by polyadenylation machinery and the PUM complex. Cancer Res; 76(24); 7231-41. ©2016 AACR.

Indexed as

Blotting, WesternFemaleGene Expression Regulation, NeoplasticGTP PhosphohydrolasesHumansMembrane ProteinsOligonucleotide Array Sequence AnalysisPolyadenylationProto-Oncogene Proteins c-junRegulatory Elements, TranscriptionalReverse Transcriptase Polymerase Chain ReactionRNA-Binding ProteinsTranscription FactorsTranscriptomeTransfectionTriple Negative Breast NeoplasmsGTP PhosphohydrolasesMembrane ProteinsNRAS protein, humanProto-Oncogene Proteins c-junpumilio protein, humanRNA-Binding ProteinsTranscription Factors

Identifiers

PMID27758885
PMCPMC5553310
OpenAlexW2530453716

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.