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NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis

Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) has been reported to play an oncogenic role in several cancers. However, the biological functions and regulatory mechanism of NUCKS1 in osteosarcoma have not been fully understood. In this study, we reported that NUCKS1 was s...

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Autores principales: Zheng, Shuo, Ji, Renchen, He, Hongtao, Li, Na, Han, Chuanchun, Han, Jian, Li, Xiaodong, Zhang, Lu, Wang, Yuan, Zhao, Wenzhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393983/
https://www.ncbi.nlm.nih.gov/pubmed/37528150
http://dx.doi.org/10.1038/s41419-023-06010-9
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author Zheng, Shuo
Ji, Renchen
He, Hongtao
Li, Na
Han, Chuanchun
Han, Jian
Li, Xiaodong
Zhang, Lu
Wang, Yuan
Zhao, Wenzhi
author_facet Zheng, Shuo
Ji, Renchen
He, Hongtao
Li, Na
Han, Chuanchun
Han, Jian
Li, Xiaodong
Zhang, Lu
Wang, Yuan
Zhao, Wenzhi
author_sort Zheng, Shuo
collection PubMed
description Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) has been reported to play an oncogenic role in several cancers. However, the biological functions and regulatory mechanism of NUCKS1 in osteosarcoma have not been fully understood. In this study, we reported that NUCKS1 was significantly increased in osteosarcoma. Depletion of NUCKS1 decreased osteosarcoma cell proliferation and metastasis in vivo and in vitro. Overexpression of NUCKS1 accelerated osteosarcoma cell aggressiveness. Mechanistically, NUCKS1 facilitated asparagine (Asn) synthesis by transcriptionally upregulating asparagine synthetase (ASNS) expression and elevating the levels of Asn in osteosarcoma cells, leading to increased cell growth and metastasis. Inhibition of ASNS or reduction of Asn decreased osteosarcoma cell aggressiveness and impaired the promoting effects of NUCKS1 on tumorigenesis and metastasis. Furthermore, we also found that by acting as a sponge for miR-4768-3p, LINC00629 promoted NUCKS1 expression. Collectively, our findings highlight the role of NUCKS1 in regulating asparagine metabolism and reveal that LINC00629 is an important regulator of NUCKS1 that contributes to NUCKS1 upregulation in osteosarcoma.
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spelling pubmed-103939832023-08-03 NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis Zheng, Shuo Ji, Renchen He, Hongtao Li, Na Han, Chuanchun Han, Jian Li, Xiaodong Zhang, Lu Wang, Yuan Zhao, Wenzhi Cell Death Dis Article Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) has been reported to play an oncogenic role in several cancers. However, the biological functions and regulatory mechanism of NUCKS1 in osteosarcoma have not been fully understood. In this study, we reported that NUCKS1 was significantly increased in osteosarcoma. Depletion of NUCKS1 decreased osteosarcoma cell proliferation and metastasis in vivo and in vitro. Overexpression of NUCKS1 accelerated osteosarcoma cell aggressiveness. Mechanistically, NUCKS1 facilitated asparagine (Asn) synthesis by transcriptionally upregulating asparagine synthetase (ASNS) expression and elevating the levels of Asn in osteosarcoma cells, leading to increased cell growth and metastasis. Inhibition of ASNS or reduction of Asn decreased osteosarcoma cell aggressiveness and impaired the promoting effects of NUCKS1 on tumorigenesis and metastasis. Furthermore, we also found that by acting as a sponge for miR-4768-3p, LINC00629 promoted NUCKS1 expression. Collectively, our findings highlight the role of NUCKS1 in regulating asparagine metabolism and reveal that LINC00629 is an important regulator of NUCKS1 that contributes to NUCKS1 upregulation in osteosarcoma. Nature Publishing Group UK 2023-08-01 /pmc/articles/PMC10393983/ /pubmed/37528150 http://dx.doi.org/10.1038/s41419-023-06010-9 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zheng, Shuo
Ji, Renchen
He, Hongtao
Li, Na
Han, Chuanchun
Han, Jian
Li, Xiaodong
Zhang, Lu
Wang, Yuan
Zhao, Wenzhi
NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
title NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
title_full NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
title_fullStr NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
title_full_unstemmed NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
title_short NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
title_sort nucks1, a linc00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10393983/
https://www.ncbi.nlm.nih.gov/pubmed/37528150
http://dx.doi.org/10.1038/s41419-023-06010-9
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