Evidence map›Paper›PMID 38871824›Full record

ArticleNature cell biology2024

Integrative analysis of ultra-deep RNA-seq reveals alternative promoter usage as a mechanism of activating oncogenic programmes during prostate cancer progression.

Meng Zhang, Martin Sjöström, Xiekui Cui, Adam Foye, Kyle Farh, Raunak Shrestha, Arian Lundberg, Ha X Dang, Haolong Li, Phillip G Febbo and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature cell biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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

11 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Meng ZhangDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1042-6294
Martin SjöströmDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2629-9966
Xiekui CuiDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.
Adam FoyeDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.
Kyle FarhIllumina, San Diego, CA, USA.
Raunak ShresthaDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1144-1413
Arian LundbergDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6630-2787
Ha X DangMcDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9342-9249
Haolong LiDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.
Phillip G FebboIllumina, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-6496-4664
Rahul AggarwalHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
Joshi J AlumkalDivision of Hematology and Oncology, University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0003-1278-0166
Eric J SmallHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
SU2C/PCF West Coast Prostate Cancer Dream Team
Christopher A MaherMcDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA.ORCID http://orcid.org/0000-0002-9035-603X
Felix Y FengDepartment of Radiation Oncology, University of California at San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0963-7687
David A QuigleyHelen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA. david.quigley@ucsf.edu.ORCID http://orcid.org/0000-0002-4726-1473

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Kate Taylor Shumate · 1999 to 2026
$209.7M
Tissue/InformaticsP50CA186786 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Ganesh S Palapattu · 2014 to 2026
$27.6M
Molecular Mechanisms of Castration Resistant Prostate Cancer Recurrence & Therapeutic StrategiesR01CA227025 · NCI · WASHINGTON UNIVERSITY · PI FENG, FELIX YI-CHUNG, MAHAJAN, NUPAM P · 2019 to 2023
$2.8M
DNA repair alterations in metastatic prostate cancer: functional and therapeutic implicationsR01CA230516 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ASHWORTH, ALAN, FENG, FELIX YI-CHUNG · 2018 to 2022
$2.7M
NCI NIH HHS P30 CA082103NCI NIH HHS P50 CA186786NCI NIH HHS R01 CA227025NCI NIH HHS R01 CA230516
6 · The paper itself

Abstract

Transcription factor (TF) proteins regulate gene activity by binding to regulatory regions, most importantly at gene promoters. Many genes have alternative promoters (APs) bound by distinct TFs. The role of differential TF activity at APs during tumour development is poorly understood. Here we show, using deep RNA sequencing in 274 biopsies of benign prostate tissue, localized prostate tumours and metastatic castration-resistant prostate cancer, that AP usage increases as tumours progress and APs are responsible for a disproportionate amount of tumour transcriptional activity. Expression of the androgen receptor (AR), the key driver of prostate tumour activity, is correlated with elevated AP usage. We identified AR, FOXA1 and MYC as potential drivers of AP activation. DNA methylation is a likely mechanism for AP activation during tumour progression and lineage plasticity. Our data suggest that prostate tumours activate APs to magnify the transcriptional impact of tumour drivers, including AR and MYC.

Indexed as

Disease ProgressionDNA MethylationGene Expression Regulation, NeoplasticHepatocyte Nuclear Factor 3-alphaPromoter Regions, GeneticProstatic NeoplasmsReceptors, AndrogenCell Line, TumorHumansMaleProstatic Neoplasms, Castration-ResistantProto-Oncogene Proteins c-mycRNA-SeqAR protein, humanFOXA1 protein, humanHepatocyte Nuclear Factor 3-alphaMYC protein, humanProto-Oncogene Proteins c-mycReceptors, Androgen

Identifiers

PMID38871824
PMCPMC11844022

What OpenQuestion holds

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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.