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Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells

Serine tRNAs (tRNA(Ser)) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at test...

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Autores principales: Santos, Mafalda, Fidalgo, Ana, Varanda, Ana Sofia, Soares, Ana Raquel, Almeida, Gabriela M., Martins, Diana, Mendes, Nuno, Oliveira, Carla, Santos, Manuel A. S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108184/
https://www.ncbi.nlm.nih.gov/pubmed/35586191
http://dx.doi.org/10.3389/fmolb.2022.809985
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author Santos, Mafalda
Fidalgo, Ana
Varanda, Ana Sofia
Soares, Ana Raquel
Almeida, Gabriela M.
Martins, Diana
Mendes, Nuno
Oliveira, Carla
Santos, Manuel A. S.
author_facet Santos, Mafalda
Fidalgo, Ana
Varanda, Ana Sofia
Soares, Ana Raquel
Almeida, Gabriela M.
Martins, Diana
Mendes, Nuno
Oliveira, Carla
Santos, Manuel A. S.
author_sort Santos, Mafalda
collection PubMed
description Serine tRNAs (tRNA(Ser)) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNA(Ser) abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNA(Ser)(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNA(Ser)(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2α dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNA(Ser)(AGA) enhanced transformation potential in vitro, and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers.
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spelling pubmed-91081842022-05-17 Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells Santos, Mafalda Fidalgo, Ana Varanda, Ana Sofia Soares, Ana Raquel Almeida, Gabriela M. Martins, Diana Mendes, Nuno Oliveira, Carla Santos, Manuel A. S. Front Mol Biosci Molecular Biosciences Serine tRNAs (tRNA(Ser)) are frequently overexpressed in tumors and associated with poor prognosis and increased risk of recurrence in breast cancer. Impairment of tRNA biogenesis and abundance also impacts proteome homeostasis, and activates protein quality control systems. Herein, we aimed at testing whether increasing tRNA(Ser) abundance could foster tumor establishment through activation of the UPR. In order to do so, firstly we confirmed that the expression of tRNA-Ser-AGA-2-1 [hereafter tRNA(Ser)(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNA(Ser)(AGA) in early stage tumorigenesis, we induced its upregulation in a non-tumoral bronchial cell line, BEAS-2B. Upregulation of this tRNA increased cellular proliferation and protein synthesis rate, driven by eIF2α dephosphorylation and ATF4 activation downstream of PERK signaling. Futhermore, tRNA(Ser)(AGA) enhanced transformation potential in vitro, and promoted the establishment of slow growing tumors with aggressive features in nude mice. Our work highlights the importance of studying tRNA deregulation on early stage tumorigenesis, as they may be potential malignancy and aggressiveness biomarkers. Frontiers Media S.A. 2022-05-02 /pmc/articles/PMC9108184/ /pubmed/35586191 http://dx.doi.org/10.3389/fmolb.2022.809985 Text en Copyright © 2022 Santos, Fidalgo, Varanda, Soares, Almeida, Martins, Mendes, Oliveira and Santos. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Santos, Mafalda
Fidalgo, Ana
Varanda, Ana Sofia
Soares, Ana Raquel
Almeida, Gabriela M.
Martins, Diana
Mendes, Nuno
Oliveira, Carla
Santos, Manuel A. S.
Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells
title Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells
title_full Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells
title_fullStr Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells
title_full_unstemmed Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells
title_short Upregulation of tRNA-Ser-AGA-2-1 Promotes Malignant Behavior in Normal Bronchial Cells
title_sort upregulation of trna-ser-aga-2-1 promotes malignant behavior in normal bronchial cells
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108184/
https://www.ncbi.nlm.nih.gov/pubmed/35586191
http://dx.doi.org/10.3389/fmolb.2022.809985
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