Upregulation of tRNA-Ser-AGA-2-1 promotes malignant behavior in normal bronchial cells
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10773/36728 |
Resumo: | Serine tRNAs (tRNASer) 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 tRNASer 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 tRNASer(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNASer(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, tRNASer(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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Upregulation of tRNA-Ser-AGA-2-1 promotes malignant behavior in normal bronchial cellstRNA deregulationCancerTumor establishmentUPRLung cancerSerine tRNAs (tRNASer) 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 tRNASer 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 tRNASer(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNASer(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, tRNASer(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 Media2023-03-30T07:54:06Z2022-01-01T00:00:00Z2022info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10773/36728eng10.3389/fmolb.2022.809985Santos, MafaldaFidalgo, AnaVaranda, Ana SofiaSoares, Ana RaquelAlmeida, Gabriela M.Martins, DianaMendes, NunoOliveira, CarlaSantos, Manuel A. S.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-02-22T12:10:04Zoai:ria.ua.pt:10773/36728Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:07:10.837591Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
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 |
spellingShingle |
Upregulation of tRNA-Ser-AGA-2-1 promotes malignant behavior in normal bronchial cells Santos, Mafalda tRNA deregulation Cancer Tumor establishment UPR Lung cancer |
title_short |
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_sort |
Upregulation of tRNA-Ser-AGA-2-1 promotes malignant behavior in normal bronchial cells |
author |
Santos, Mafalda |
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_role |
author |
author2 |
Fidalgo, Ana Varanda, Ana Sofia Soares, Ana Raquel Almeida, Gabriela M. Martins, Diana Mendes, Nuno Oliveira, Carla Santos, Manuel A. S. |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Santos, Mafalda Fidalgo, Ana Varanda, Ana Sofia Soares, Ana Raquel Almeida, Gabriela M. Martins, Diana Mendes, Nuno Oliveira, Carla Santos, Manuel A. S. |
dc.subject.por.fl_str_mv |
tRNA deregulation Cancer Tumor establishment UPR Lung cancer |
topic |
tRNA deregulation Cancer Tumor establishment UPR Lung cancer |
description |
Serine tRNAs (tRNASer) 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 tRNASer 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 tRNASer(AGA)] was upregulated by 1.79-fold in Stage I NSCLC tumors when compared to normal adjacent tissue. To study the impact of tRNASer(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, tRNASer(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. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-01-01T00:00:00Z 2022 2023-03-30T07:54:06Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10773/36728 |
url |
http://hdl.handle.net/10773/36728 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.3389/fmolb.2022.809985 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
publisher.none.fl_str_mv |
Frontiers Media |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799137727275335680 |