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Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness

N6‐methyladenosine (m(6)A) and its regulatory proteins have been associated with tumorigenesis in several cancer types. However, knowledge on the mechanistic network related to m(6)A in bladder cancer (BlCa) is rather limited, requiring further investigation of its functional role. We aimed to uncov...

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Detalles Bibliográficos
Autores principales: Guimarães‐Teixeira, Catarina, Lobo, João, Miranda‐Gonçalves, Vera, Barros‐Silva, Daniela, Martins‐Lima, Cláudia, Monteiro‐Reis, Sara, Sequeira, José Pedro, Carneiro, Isa, Correia, Margareta P., Henrique, Rui, Jerónimo, Carmen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9067151/
https://www.ncbi.nlm.nih.gov/pubmed/35048498
http://dx.doi.org/10.1002/1878-0261.13181
Descripción
Sumario:N6‐methyladenosine (m(6)A) and its regulatory proteins have been associated with tumorigenesis in several cancer types. However, knowledge on the mechanistic network related to m(6)A in bladder cancer (BlCa) is rather limited, requiring further investigation of its functional role. We aimed to uncover the biological role of m(6)A and related proteins in BlCa and understand how this influences tumor aggressiveness. N6‐adenosine‐methyltransferase catalytic subunit (METTL3), N6‐adenosine‐methyltransferase noncatalytic subunit (METTL14), protein virilizer homolog (VIRMA), and RNA demethylase ALKBH5 (ALKBH5) had significantly lower expression levels in BlCa compared to that in normal urothelium. METTL14 knockdown led to disruption of the remaining methyltransferase complex and a decrease in m(6)A abundance, as well as overall reduced tumor aggressiveness (decreased cell invasion and migration capacity and increased apoptosis). Furthermore, in vivo, METTL14 knockdown caused tumor size reduction. Collectively, we propose methyltransferase METTL14 as a key component for m(6)A RNA deposit and that it is closely related to BlCa progression, playing an important role in tumor aggressiveness. These data contribute to a better understanding of the m(6)A writer complex, which might constitute an appealing therapeutic target.