RT Journal Article
T1 CRISPR/Cas9 screenings unearth protein arginine methyltransferase 7 as a novel essential gene in prostate cancer metastasis
A1 Rodrigo Faus, María
A1 Vincelle-Nieto, África
A1 Vidal, Natalia
A1 Puente, Javier
A1 Saiz-Pardo Sanz, Melchor
A1 López-García, Alejandra
A1 Mendiburu-Eliçabe, Marina
A1 Palao, Nerea
A1 Baquero, Cristina
A1 Linzoain-Agos, Paula
A1 Cuesta Martínez, Ángel
A1 Qu, Hui Qi
A1 Hakonarson, Hakon
A1 Musteanu, Mónica Andrea
A1 Reyes Palomares, Armando Adolfo
A1 Porras Gallo, María Almudena
A1 Bragado Domingo, Paloma
A1 Gutiérrez Uzquiza, Álvaro
AB 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.
PB Elsevier
SN 0304-3835
YR 2024
FD 2024-03-02
LK https://hdl.handle.net/20.500.14352/103575
UL https://hdl.handle.net/20.500.14352/103575
LA eng
NO 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.
NO Comunidad de Madrid
NO Ministerio de Ciencia e Innovación (España)
DS Docta Complutense
RD 1 jul 2024