CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis

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dc.contributor.authorRodrigo Faus, María
dc.contributor.authorVincelle-Nieto, África
dc.contributor.authorVidal, Natalia
dc.contributor.authorPuente, Javier
dc.contributor.authorSaiz-Pardo Sanz, Melchor
dc.contributor.authorLópez-García, Alejandra
dc.contributor.authorMendiburu-Eliçabe Garganta, Marina
dc.contributor.authorPalao, Nerea
dc.contributor.authorBaquero, Cristina
dc.contributor.authorLinzoain-Agos, Paula
dc.contributor.authorCuesta Martínez, Ángel
dc.contributor.authorQu, Hui Qi
dc.contributor.authorHakonarson, Hakon
dc.contributor.authorMusteanu, Mónica Andrea
dc.contributor.authorReyes Palomares, Armando Adolfo
dc.contributor.authorPorras Gallo, María Almudena
dc.contributor.authorBragado Domingo, Paloma
dc.contributor.authorGutiérrez Uzquiza, Álvaro
dc.date.accessioned2024-04-26T13:51:00Z
dc.date.available2024-04-26T13:51:00Z
dc.date.issued2024-03-02
dc.descriptionCredit authorship contribution statement: Maria Rodrigo-Faus: Writing – review & editing, Writing – original draft, Visualization, Validation, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Africa Vincelle-Nieto: Writing – original draft, Visualization, Software, Methodology, Formal analysis. Natalia Vidal: Resources. Javier Puente: Resources. Melchor Saiz-Pardo: Resources, Investigation. Alejandra Lopez-Garcia: Resources, Methodology, Investigation. Marina Mendiburu-Eliçabe: Visualization, Formal analysis, Data curation. Nerea Palao: Visualization, Conceptualization. Cristina Baquero: Methodology. Paula Linzoain-Agos: Investigation, Methodology, Writing – review & editing. Angel M. Cuesta: Visualization, Methodology. Hui-Qi Qu: Visualization, Methodology, Formal analysis, Data curation. Hakon Hakonarson: Supervision, Conceptualization. Monica Musteanu: Validation, Supervision, Resources, Methodology. Armando ReyesPalomares: Writing – review & editing, Visualization, Validation, Methodology, Formal analysis, Data curation, Conceptualization. Almudena Porras: Writing – review & editing, Supervision, Conceptualization. Paloma Bragado: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Project administration, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. Alvaro Gutierrez-Uzquiza: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization.en
dc.description.abstractDue to the limited effectiveness of current treatments, the survival rate of patients with metastatic castration-resistant prostate cancer (mCRPC) is significantly reduced. Consequently, it is imperative to identify novel therapeutic targets for managing these patients. Since the invasive ability of cells is crucial for establishing and maintaining metastasis, the aim of this study was to identify the essential regulators of invasive abilities of mCRPC cells by conducting two independent high-throughput CRISPR/Cas9 screenings. Furthermore, some of the top hits were validated using siRNA technology, with protein arginine methyltransferase 7 (PRMT7) emerging as the most promising candidate. We demonstrated that its inhibition or depletion via genetic or pharmacological approaches significantly reduces invasive, migratory and proliferative abilities of mCRPC cells in vitro. Moreover, we confirmed that PRMT7 ablation reduces cell dissemination in chicken chorioallantoic membrane and mouse xenograft assays. Molecularly, PRMT7 reprograms the expression of several adhesion molecules by methylating various transcription factors, such as FoxK1, resulting in the loss of adhesion from the primary tumor and increased motility of mCRPC cells. Furthermore, PRMT7 higher expression correlates with tumor aggressivity and poor overall survival in prostate cancer patients. Thus, this study demonstrates that PRMT7 is a potential therapeutic target and potential biomarker for mPCa.en
dc.description.departmentSección Deptal. de Bioquímica y Biología Molecular (Veterinaria)
dc.description.departmentSección Deptal. de Bioquímica y Biología Molecular (Farmacia)
dc.description.facultyFac. de Veterinaria
dc.description.refereedTRUE
dc.description.sponsorshipComunidad de Madrid
dc.description.sponsorshipMinisterio de Ciencia, Innovación y Universidades (España)
dc.description.statuspub
dc.identifier.doi10.1016/j.canlet.2024.216776
dc.identifier.essn1872-7980
dc.identifier.issn0304-3835
dc.identifier.officialurlhttps://doi.org/10.1016/j.canlet.2024.216776
dc.identifier.urihttps://hdl.handle.net/20.500.14352/103575
dc.issue.number216776
dc.journal.titleCancer Letters
dc.language.isoeng
dc.publisherElsevier
dc.relation.projectIDinfo:eu-repo/grantAgreement/CAM/2017- T1/BMD-5468
dc.relation.projectIDinfo:eu-repo/grantAgreement/CAM/2021-5A/BMD-20956
dc.relation.projectIDinfo:eu-repo/grantAgreement/MCIN/AEI/10.13039/ 501100011033
dc.rightsAttribution 4.0 Internationalen
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.cdu577.2
dc.subject.keywordProstate cancer
dc.subject.keywordMetastasis
dc.subject.keywordInvasion
dc.subject.keywordPRMT7
dc.subject.keywordAdhesion
dc.subject.ucmBioquímica (Farmacia)
dc.subject.ucmBiología molecular (Farmacia)
dc.subject.unesco2403 Bioquímica
dc.titleCRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasisen
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number588
dspace.entity.typePublication
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CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis
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