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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |