Cargando…

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...

Descripción completa

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
_version_ 1784699945165520896
author 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
author_facet 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
author_sort Guimarães‐Teixeira, Catarina
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9067151
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-90671512022-05-09 Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness 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 Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2022-03-24 2022-05 /pmc/articles/PMC9067151/ /pubmed/35048498 http://dx.doi.org/10.1002/1878-0261.13181 Text en © 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
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
Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness
title Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness
title_full Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness
title_fullStr Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness
title_full_unstemmed Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness
title_short Downregulation of m(6)A writer complex member METTL14 in bladder urothelial carcinoma suppresses tumor aggressiveness
title_sort downregulation of m(6)a writer complex member mettl14 in bladder urothelial carcinoma suppresses tumor aggressiveness
topic Research Articles
url 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
work_keys_str_mv AT guimaraesteixeiracatarina downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT lobojoao downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT mirandagoncalvesvera downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT barrossilvadaniela downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT martinslimaclaudia downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT monteiroreissara downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT sequeirajosepedro downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT carneiroisa downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT correiamargaretap downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT henriquerui downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness
AT jeronimocarmen downregulationofm6awritercomplexmembermettl14inbladderurothelialcarcinomasuppressestumoraggressiveness