NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis
Abstract 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 NUC...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-08-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-023-06010-9 |
| _version_ | 1797752631521705984 |
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| author | Shuo Zheng Renchen Ji Hongtao He Na Li Chuanchun Han Jian Han Xiaodong Li Lu Zhang Yuan Wang Wenzhi Zhao |
| author_facet | Shuo Zheng Renchen Ji Hongtao He Na Li Chuanchun Han Jian Han Xiaodong Li Lu Zhang Yuan Wang Wenzhi Zhao |
| author_sort | Shuo Zheng |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-12T17:06:14Z |
| format | Article |
| id | doaj.art-98d76ad09a38421f8dcdac9d8e47c75f |
| institution | Directory Open Access Journal |
| issn | 2041-4889 |
| language | English |
| last_indexed | 2024-03-12T17:06:14Z |
| publishDate | 2023-08-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj.art-98d76ad09a38421f8dcdac9d8e47c75f2023-08-06T11:26:07ZengNature Publishing GroupCell Death and Disease2041-48892023-08-0114811510.1038/s41419-023-06010-9NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesisShuo Zheng0Renchen Ji1Hongtao He2Na Li3Chuanchun Han4Jian Han5Xiaodong Li6Lu Zhang7Yuan Wang8Wenzhi Zhao9The Second Affiliated Hospital, Dalian Medical UniversityThe Second Affiliated Hospital, Dalian Medical UniversityThe Second Affiliated Hospital, Dalian Medical UniversityNational-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical UniversityInstitute of Cancer Stem Cell, Dalian Medical UniversityDepartment of Orthopedics, The Third People’s Hospital of Dalian, Dalian Medical UniversityThe Second Affiliated Hospital, Dalian Medical UniversityThe Second Affiliated Hospital, Dalian Medical UniversityThe Second Affiliated Hospital, Dalian Medical UniversityThe Second Affiliated Hospital, Dalian Medical UniversityAbstract 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.https://doi.org/10.1038/s41419-023-06010-9 |
| spellingShingle | Shuo Zheng Renchen Ji Hongtao He Na Li Chuanchun Han Jian Han Xiaodong Li Lu Zhang Yuan Wang Wenzhi Zhao NUCKS1, a LINC00629-upregulated gene, facilitated osteosarcoma progression and metastasis by elevating asparagine synthesis Cell Death and Disease |
| 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 |
| url | https://doi.org/10.1038/s41419-023-06010-9 |
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