CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis
dc.contributor.author | Rodrigo Faus, María | |
dc.contributor.author | Vincelle-Nieto, África | |
dc.contributor.author | Vidal, Natalia | |
dc.contributor.author | Puente, Javier | |
dc.contributor.author | Saiz-Pardo Sanz, Melchor | |
dc.contributor.author | López-García, Alejandra | |
dc.contributor.author | Mendiburu-Eliçabe Garganta, Marina | |
dc.contributor.author | Palao, Nerea | |
dc.contributor.author | Baquero, Cristina | |
dc.contributor.author | Linzoain-Agos, Paula | |
dc.contributor.author | Cuesta Martínez, Ángel | |
dc.contributor.author | Qu, Hui Qi | |
dc.contributor.author | Hakonarson, Hakon | |
dc.contributor.author | Musteanu, Mónica Andrea | |
dc.contributor.author | Reyes Palomares, Armando Adolfo | |
dc.contributor.author | Porras Gallo, María Almudena | |
dc.contributor.author | Bragado Domingo, Paloma | |
dc.contributor.author | Gutiérrez Uzquiza, Álvaro | |
dc.date.accessioned | 2024-04-26T13:51:00Z | |
dc.date.available | 2024-04-26T13:51:00Z | |
dc.date.issued | 2024-03-02 | |
dc.description | Credit 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.abstract | Due 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.department | Sección Deptal. de Bioquímica y Biología Molecular (Veterinaria) | |
dc.description.department | Sección Deptal. de Bioquímica y Biología Molecular (Farmacia) | |
dc.description.faculty | Fac. de Veterinaria | |
dc.description.refereed | TRUE | |
dc.description.sponsorship | Comunidad de Madrid | |
dc.description.sponsorship | Ministerio de Ciencia, Innovación y Universidades (España) | |
dc.description.status | pub | |
dc.identifier.doi | 10.1016/j.canlet.2024.216776 | |
dc.identifier.essn | 1872-7980 | |
dc.identifier.issn | 0304-3835 | |
dc.identifier.officialurl | https://doi.org/10.1016/j.canlet.2024.216776 | |
dc.identifier.uri | https://hdl.handle.net/20.500.14352/103575 | |
dc.issue.number | 216776 | |
dc.journal.title | Cancer Letters | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.projectID | info:eu-repo/grantAgreement/CAM/2017- T1/BMD-5468 | |
dc.relation.projectID | info:eu-repo/grantAgreement/CAM/2021-5A/BMD-20956 | |
dc.relation.projectID | info:eu-repo/grantAgreement/MCIN/AEI/10.13039/ 501100011033 | |
dc.rights | Attribution 4.0 International | en |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject.cdu | 577.2 | |
dc.subject.keyword | Prostate cancer | |
dc.subject.keyword | Metastasis | |
dc.subject.keyword | Invasion | |
dc.subject.keyword | PRMT7 | |
dc.subject.keyword | Adhesion | |
dc.subject.ucm | Bioquímica (Farmacia) | |
dc.subject.ucm | Biología molecular (Farmacia) | |
dc.subject.unesco | 2403 Bioquímica | |
dc.title | CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis | en |
dc.type | journal article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 588 | |
dspace.entity.type | Publication | |
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relation.isAuthorOfPublication.latestForDiscovery | 5d34fc64-0ace-4de7-8dd9-6735bf7881dd |
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