Evidence map›Paper›PMID 30100395›Full record

ArticleEBioMedicine2018

A novel mechanism of SRRM4 in promoting neuroendocrine prostate cancer development via a pluripotency gene network.

Ahn R Lee, Yu Gan, Yuxin Tang, Xuesen Dong

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

Article in EBioMedicine, 2018. 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 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
4.9field-weighted citation impact, top 4% 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

40 citing papers in PubMed, 56 citations in OpenAlex.

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  13. Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 2 countries.

Ahn R LeeVancouver Prostate Centre, Department of Urologic Sciences, The University of British Columbia, 2660 Oak Street, Vancouver, BC, Canada. Electronic address: alee@prostatecentre.com.
Yu GanVancouver Prostate Centre, Department of Urologic Sciences, The University of British Columbia, 2660 Oak Street, Vancouver, BC, Canada; Xiangya Hospital, Department of Urology, Central South University, Changsha, Hunan, China; Third Xiangya Hospital, Department of Urology, Central South University, Changsha, Hunan, China. Electronic address: ygan@prostatecentre.com.
Yuxin TangThird Xiangya Hospital, Department of Urology, Central South University, Changsha, Hunan, China. Electronic address: tangyuxin@csu.edu.cn.
Xuesen DongVancouver Prostate Centre, Department of Urologic Sciences, The University of British Columbia, 2660 Oak Street, Vancouver, BC, Canada. Electronic address: xdong@prostatecentre.com.
University of British Columbia · CAThird Xiangya Hospital · CNXiangya Hospital Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundProstate adenocarcinoma (AdPC) cells can undergo lineage switching to neuroendocrine cells and develop into therapy-resistant neuroendocrine prostate cancer (NEPC). While genomic/epigenetic alterations are shown to induce neuroendocrine differentiation via an intermediate stem-like state, RNA splicing factor SRRM4 can transform AdPC cells into NEPC xenografts through a direct neuroendocrine transdifferentiation mechanism. Whether SRRM4 can also regulate a stem-cell gene network for NEPC development remains unclear.

methodsMultiple AdPC cell models were transduced by lentiviral vectors encoding SRRM4. SRRM4-mediated RNA splicing and neuroendocrine differentiation of cells and xenografts were determined by qPCR, immunoblotting, and immunohistochemistry. Cell morphology, proliferation, and colony formation rates were also studied. SRRM4 transcriptome in the DU145 cell model was profiled by AmpliSeq and analyzed by gene enrichment studies.

findingsSRRM4 induces an overall NEPC-specific RNA splicing program in multiple cell models but creates heterogeneous transcriptomes. SRRM4-transduced DU145 cells present the most dramatic neuronal morphological changes, accelerated cell proliferation, and enhanced resistance to apoptosis. The derived xenografts show classic phenotypes similar to clinical NEPC. Whole transcriptome analyses further reveal that SRRM4 induces a pluripotency gene network consisting of the stem-cell differentiation gene, SOX2. While SRRM4 overexpression enhances SOX2 expression in both time- and dose-dependent manners in DU145 cells, RNA depletion of SOX2 compromises SRRM4-mediated stimulation of pluripotency genes. More importantly, this SRRM4-SOX2 axis is present in a subset of NEPC patient cohorts, patient-derived xenografts, and clinically relevant transgenic mouse models.

interpretationWe report a novel mechanism by which SRRM4 drives NEPC progression via a pluripotency gene network. FUND: Canadian Institutes of Health Research, National Nature Science Foundation of China, and China Scholar Council.

Indexed as

Gene Regulatory NetworksAnimalsCarcinogenesisCarcinoma, NeuroendocrineCell DifferentiationCell Line, TumorGene Expression Regulation, NeoplasticHumansMaleMiceModels, BiologicalNerve Tissue ProteinsPluripotent Stem CellsProstatic NeoplasmsSOXB1 Transcription FactorsTranscriptomeNerve Tissue ProteinsSOXB1 Transcription FactorsSRRM4 protein, humanlineage plasticityRNA splicingSRRM4transcriptometreatment-resistant mechanisms

Identifiers

PMID30100395
PMCPMC6154886
OpenAlexW2886821920

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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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.