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First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes

Cancer-associated factors have been largely identified in the understanding of tumorigenesis and progression. However, aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) have so far been neglected in cancer research due to their canonical activities in protein translation and synthesis. FARSA, the al...

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Detalles Bibliográficos
Autores principales: Feng, Min, Yang, Kun, Wang, Jia, Li, Guilan, Zhang, Han
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865697/
https://www.ncbi.nlm.nih.gov/pubmed/36675119
http://dx.doi.org/10.3390/ijms24021608
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author Feng, Min
Yang, Kun
Wang, Jia
Li, Guilan
Zhang, Han
author_facet Feng, Min
Yang, Kun
Wang, Jia
Li, Guilan
Zhang, Han
author_sort Feng, Min
collection PubMed
description Cancer-associated factors have been largely identified in the understanding of tumorigenesis and progression. However, aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) have so far been neglected in cancer research due to their canonical activities in protein translation and synthesis. FARSA, the alpha subunit of the phenylalanyl-tRNA synthetase is elevated across many cancer types, but its function in mantle cell lymphoma (MCL) remains undetermined. Herein, we found the lowest levels of FARSA in patients with MCL compared with other subtypes of lymphomas, and the same lower levels of FARSA were observed in chemoresistant MCL cell lines. Unexpectedly, despite the essential catalytic roles of FARSA, knockdown of FARSA in MCL cells did not lead to cell death but resulted in accelerated cell proliferation and cell cycle, whereas overexpression of FARSA induced remarkable cell-cycle arrest and overwhelming apoptosis. Further RNA sequencing (RNA-seq) analysis and validation experiments confirmed a strong connection between FARSA and cell cycle in MCL cells. Importantly, FARSA leads to the alteration of cell cycle and survival via both PI3K-AKT and FOXO1-RAG1 axes, highlighting a FARSA-mediated regulatory network in MCL cells. Our findings, for the first time, reveal the noncanonical roles of FARSA in MCL cells, and provide novel insights into understanding the pathogenesis and progression of B-cell malignancies.
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spelling pubmed-98656972023-01-22 First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes Feng, Min Yang, Kun Wang, Jia Li, Guilan Zhang, Han Int J Mol Sci Article Cancer-associated factors have been largely identified in the understanding of tumorigenesis and progression. However, aminoacyl-transfer RNA (tRNA) synthetases (aaRSs) have so far been neglected in cancer research due to their canonical activities in protein translation and synthesis. FARSA, the alpha subunit of the phenylalanyl-tRNA synthetase is elevated across many cancer types, but its function in mantle cell lymphoma (MCL) remains undetermined. Herein, we found the lowest levels of FARSA in patients with MCL compared with other subtypes of lymphomas, and the same lower levels of FARSA were observed in chemoresistant MCL cell lines. Unexpectedly, despite the essential catalytic roles of FARSA, knockdown of FARSA in MCL cells did not lead to cell death but resulted in accelerated cell proliferation and cell cycle, whereas overexpression of FARSA induced remarkable cell-cycle arrest and overwhelming apoptosis. Further RNA sequencing (RNA-seq) analysis and validation experiments confirmed a strong connection between FARSA and cell cycle in MCL cells. Importantly, FARSA leads to the alteration of cell cycle and survival via both PI3K-AKT and FOXO1-RAG1 axes, highlighting a FARSA-mediated regulatory network in MCL cells. Our findings, for the first time, reveal the noncanonical roles of FARSA in MCL cells, and provide novel insights into understanding the pathogenesis and progression of B-cell malignancies. MDPI 2023-01-13 /pmc/articles/PMC9865697/ /pubmed/36675119 http://dx.doi.org/10.3390/ijms24021608 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Feng, Min
Yang, Kun
Wang, Jia
Li, Guilan
Zhang, Han
First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes
title First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes
title_full First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes
title_fullStr First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes
title_full_unstemmed First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes
title_short First Report of FARSA in the Regulation of Cell Cycle and Survival in Mantle Cell Lymphoma Cells via PI3K-AKT and FOXO1-RAG1 Axes
title_sort first report of farsa in the regulation of cell cycle and survival in mantle cell lymphoma cells via pi3k-akt and foxo1-rag1 axes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9865697/
https://www.ncbi.nlm.nih.gov/pubmed/36675119
http://dx.doi.org/10.3390/ijms24021608
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