Evidence map›Paper›PMID 25369795›Full record

ArticleBMC cancer2014

RNA-seq profiling of a radiation resistant and radiation sensitive prostate cancer cell line highlights opposing regulation of DNA repair and targets for radiosensitization.

Arabella Young, Rachael Berry, Adele F Holloway, Nicholas B Blackburn, Joanne L Dickinson, Marketa Skala, Jessica L Phillips, Kate H Brettingham-Moore

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

22 citing papers in PubMed, 40 citations in OpenAlex.

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  12. CDC6 is up-regulated and a poor prognostic signature in glioblastoma multiforme.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021
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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 2 institutions in 1 country.

Arabella Young
Rachael Berry
Adele F Holloway
Nicholas B Blackburn
Joanne L Dickinson
Marketa Skala
Jessica L Phillips
Kate H Brettingham-MooreSchool of Medicine, University of Tasmania, Private Bag 23, Hobart, TAS 7000, Australia. khmoore@utas.edu.au.
University of Tasmania · AURoyal Hobart Hospital · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRadiotherapy is a chosen treatment option for prostate cancer patients and while some tumours respond well, up to 50% of patients may experience tumour recurrence. Identification of functionally relevant predictive biomarkers for radioresponse in prostate cancer would enable radioresistant patients to be directed to more appropriate treatment options, avoiding the side-effects of radiotherapy.

methodsUsing an in vitro model to screen for novel biomarkers of radioresistance, transcriptome analysis of a radioresistant (PC-3) and radiosensitive (LNCaP) prostate cancer cell line was performed. Following pathway analysis candidate genes were validated using qRT-PCR. The DNA repair pathway in radioresistant PC-3 cells was then targeted for radiation sensitization using the PARP inhibitor, niacinimide.

resultsOpposing regulation of a DNA repair and replication pathway was observed between PC-3 and LNCaP cells from RNA-seq analysis. Candidate genes BRCA1, RAD51, FANCG, MCM7, CDC6 and ORC1 were identified as being significantly differentially regulated post-irradiation. qRT-PCR validation confirmed BRCA1, RAD51 and FANCG as being significantly differentially regulated at 24 hours post radiotherapy (p-value =0.003, 0.045 and 0.003 respectively). While the radiosensitive LNCaP cells down-regulated BRCA1, FANCG and RAD51, the radioresistant PC-3 cell line up-regulated these candidates to promote cell survival post-radiotherapy and a similar trend was observed for MCM7, CDC6 and ORC1. Inhibition of DNA repair using niacinamide sensitised the radioresistant cells to irradiation, reducing cell survival at 2 Gy from 66% to 44.3% (p-value =0.02).

conclusionsThese findings suggest that the DNA repair candidates identified via RNA-seq hold potential as both targets for radiation sensitization and predictive biomarkers in prostate cancer.

Indexed as

Biomarkers, TumorBRCA1 ProteinCell Cycle ProteinsCell Line, TumorCell SurvivalDNA RepairDown-RegulationEnzyme InhibitorsFanconi Anemia Complementation Group G ProteinGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMaleMinichromosome Maintenance Complex Component 7NiacinamideNuclear ProteinsBiomarkers, TumorBRCA1 ProteinCDC6 protein, humanCell Cycle ProteinsEnzyme InhibitorsFANCG protein, humanFanconi Anemia Complementation Group G ProteinMCM7 protein, humanMinichromosome Maintenance Complex Component 7NiacinamideNuclear ProteinsORC1 protein, humanOrigin Recognition ComplexPoly(ADP-ribose) Polymerase InhibitorsRad51 RecombinaseRadiation-Sensitizing AgentsRNA, Messenger

Identifiers

PMID25369795
PMCPMC4233036
OpenAlexW2010773546

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.