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METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development

BACKGROUND: The posttranscriptional modifications of transfer RNA (tRNA) are critical for all aspects of the tRNA function and have been implicated in the tumourigenesis and progression of many human cancers. By contrast, the biological functions of methyltransferase‐like 1 (METTL1)‐regulated m(7)G...

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Autores principales: Ying, Xiaoling, Liu, Bixia, Yuan, Zusen, Huang, Yapeng, Chen, Cong, Jiang, Xu, Zhang, Haiqing, Qi, Defeng, Yang, Shulan, Lin, Shuibin, Luo, Junhang, Ji, Weidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694502/
https://www.ncbi.nlm.nih.gov/pubmed/34936728
http://dx.doi.org/10.1002/ctm2.675
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author Ying, Xiaoling
Liu, Bixia
Yuan, Zusen
Huang, Yapeng
Chen, Cong
Jiang, Xu
Zhang, Haiqing
Qi, Defeng
Yang, Shulan
Lin, Shuibin
Luo, Junhang
Ji, Weidong
author_facet Ying, Xiaoling
Liu, Bixia
Yuan, Zusen
Huang, Yapeng
Chen, Cong
Jiang, Xu
Zhang, Haiqing
Qi, Defeng
Yang, Shulan
Lin, Shuibin
Luo, Junhang
Ji, Weidong
author_sort Ying, Xiaoling
collection PubMed
description BACKGROUND: The posttranscriptional modifications of transfer RNA (tRNA) are critical for all aspects of the tRNA function and have been implicated in the tumourigenesis and progression of many human cancers. By contrast, the biological functions of methyltransferase‐like 1 (METTL1)‐regulated m(7)G tRNA modification in bladder cancer (BC) remain obscure. RESULTS: In this research, we show that METTL1 was highly expressed in BC, and its level was correlated with poor patient prognosis. Silencing METTL1 suppresses the proliferation, migration and invasion of BC cells in vitro and in vivo. Multi‐omics analysis reveals that METTL1‐mediated m(7)G tRNA modification altered expression of certain target genes, including EGFR/EFEMP1. Mechanistically, METTL1 regulates the translation of EGFR/EFEMP1 via modifying certain tRNAs. Furthermore, forced expression of EGFR/EFEMP1 partially rescues the effect of METTL1 deletion on BC cells. CONCLUSIONS: Our findings demonstrate the oncogenic role of METTL1 and the pathological significance of the METTL1‐m(7)G‐EGFR/EFEMP1 axis in the BC development, thus providing potential therapeutic targets for the BC treatment.
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spelling pubmed-86945022022-01-04 METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development Ying, Xiaoling Liu, Bixia Yuan, Zusen Huang, Yapeng Chen, Cong Jiang, Xu Zhang, Haiqing Qi, Defeng Yang, Shulan Lin, Shuibin Luo, Junhang Ji, Weidong Clin Transl Med Research Articles BACKGROUND: The posttranscriptional modifications of transfer RNA (tRNA) are critical for all aspects of the tRNA function and have been implicated in the tumourigenesis and progression of many human cancers. By contrast, the biological functions of methyltransferase‐like 1 (METTL1)‐regulated m(7)G tRNA modification in bladder cancer (BC) remain obscure. RESULTS: In this research, we show that METTL1 was highly expressed in BC, and its level was correlated with poor patient prognosis. Silencing METTL1 suppresses the proliferation, migration and invasion of BC cells in vitro and in vivo. Multi‐omics analysis reveals that METTL1‐mediated m(7)G tRNA modification altered expression of certain target genes, including EGFR/EFEMP1. Mechanistically, METTL1 regulates the translation of EGFR/EFEMP1 via modifying certain tRNAs. Furthermore, forced expression of EGFR/EFEMP1 partially rescues the effect of METTL1 deletion on BC cells. CONCLUSIONS: Our findings demonstrate the oncogenic role of METTL1 and the pathological significance of the METTL1‐m(7)G‐EGFR/EFEMP1 axis in the BC development, thus providing potential therapeutic targets for the BC treatment. John Wiley and Sons Inc. 2021-12-22 /pmc/articles/PMC8694502/ /pubmed/34936728 http://dx.doi.org/10.1002/ctm2.675 Text en © 2021 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics 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
Ying, Xiaoling
Liu, Bixia
Yuan, Zusen
Huang, Yapeng
Chen, Cong
Jiang, Xu
Zhang, Haiqing
Qi, Defeng
Yang, Shulan
Lin, Shuibin
Luo, Junhang
Ji, Weidong
METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development
title METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development
title_full METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development
title_fullStr METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development
title_full_unstemmed METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development
title_short METTL1‐m(7)G‐EGFR/EFEMP1 axis promotes the bladder cancer development
title_sort mettl1‐m(7)g‐egfr/efemp1 axis promotes the bladder cancer development
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8694502/
https://www.ncbi.nlm.nih.gov/pubmed/34936728
http://dx.doi.org/10.1002/ctm2.675
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