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NUCKS1，一个受 LINC00629 上调的基因，通过提高天冬酰胺合成促进骨肉瘤的进展和转移。

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

机构信息

The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning, 116044, P.R. China.

Institute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, 116044, P.R. China.

出版信息

Cell Death Dis. 2023 Aug 1;14(8):489. doi: 10.1038/s41419-023-06010-9.

DOI:10.1038/s41419-023-06010-9
PMID:37528150
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10393983/
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.

摘要

核普遍存在的酪蛋白和细胞周期蛋白依赖性激酶底物 1（NUCKS1）已被报道在几种癌症中发挥致癌作用。然而，NUCKS1 在骨肉瘤中的生物学功能和调节机制尚未完全阐明。在本研究中，我们报道 NUCKS1 在骨肉瘤中显著增加。NUCKS1 的耗竭降低了骨肉瘤细胞在体内和体外的增殖和转移。过表达 NUCKS1 加速了骨肉瘤细胞的侵袭性。在机制上，NUCKS1 通过转录上调天冬酰胺合成酶（ASNS）的表达并提高骨肉瘤细胞中天冬酰胺的水平，促进天冬酰胺的合成，从而增加细胞生长和转移。ASNS 的抑制或天冬酰胺的减少降低了骨肉瘤细胞的侵袭性，并削弱了 NUCKS1 对肿瘤发生和转移的促进作用。此外，我们还发现，LINC00629 通过作为 miR-4768-3p 的海绵，促进 NUCKS1 的表达。总之，我们的研究结果强调了 NUCKS1 在调节天冬酰胺代谢中的作用，并揭示了 LINC00629 是 NUCKS1 的一个重要调节因子，有助于骨肉瘤中 NUCKS1 的上调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/bef06a4f06c6/41419_2023_6010_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/ba4855b5a2f9/41419_2023_6010_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/9a7bee5f3aa3/41419_2023_6010_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/9162c8156e3e/41419_2023_6010_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/c552546359fe/41419_2023_6010_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/85a297078825/41419_2023_6010_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/7be435e4e2a8/41419_2023_6010_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/ad921094dccf/41419_2023_6010_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/43b80e821ba1/41419_2023_6010_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/bef06a4f06c6/41419_2023_6010_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/ba4855b5a2f9/41419_2023_6010_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/9a7bee5f3aa3/41419_2023_6010_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/9162c8156e3e/41419_2023_6010_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/c552546359fe/41419_2023_6010_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/85a297078825/41419_2023_6010_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/7be435e4e2a8/41419_2023_6010_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/ad921094dccf/41419_2023_6010_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/43b80e821ba1/41419_2023_6010_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1331/10393983/bef06a4f06c6/41419_2023_6010_Fig9_HTML.jpg

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