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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-9865697 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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