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On-line Access: 2024-05-10

Received: 2023-04-06

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Crosschecked: 2024-05-10

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Yu ZHANG

0000-0002-3409-5496

Xinliang GU

0009-0001-8118-5347

Yuejiao HUANG

0000-0001-6532-9497

Shaoqing JU

0000-0001-7448-2020

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Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.5 P.438-450

http://doi.org/10.1631/jzus.B2300215


Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB


Author(s):  Yu ZHANG, Xinliang GU, Yang LI, Xun LI, Yuejiao HUANG, Shaoqing JU

Affiliation(s):  Medical School of Nantong University, Nantong University, Nantong 226001, China; more

Corresponding email(s):   huangyuejiao20@126.com, jsq814@hotmail.com

Key Words:  Transfer RNA (tRNA)‍, -derived small RNA (tsRNA), Gastric cancer (GC), Acyl-coenzyme A dehydrogenase short/branched chain (ACADSB), Molecular mechanism, Treatment, Ferroptosis


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Yu ZHANG, Xinliang GU, Yang LI, Xun LI, Yuejiao HUANG, Shaoqing JU. Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB[J]. Journal of Zhejiang University Science B, 2024, 25(5): 438-450.

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journal="Journal of Zhejiang University Science B",
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year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300215"
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%T Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB
%A Yu ZHANG
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%A Yuejiao HUANG
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A1 - Yu ZHANG
A1 - Xinliang GU
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A1 - Xun LI
A1 - Yuejiao HUANG
A1 - Shaoqing JU
J0 - Journal of Zhejiang University Science B
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Abstract: 
gastric cancer (GC) is one of the most common gastrointestinal tumors. As a newly discovered type of non-coding RNAs, transfer RNA (tRNA)‍;-derived small RNAs (tsRNAs) play a dual biological role in cancer. Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC. In this work, we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation, migration, and invasion of GC cells in vitro. The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3' untranslated region (UTR) site of acyl-coenzyme A dehydrogenase short/branched chain (ACADSB). In addition, ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells. Next, we used Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis. Finally, we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level, as well as the changes in reactive oxygen species (ROS) levels by flow cytometry. In summary, this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB, thereby promoting GC progression. It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens up new possibilities for treatment.

转移RNA衍生片段tRF-23-Q99P9P9NDD通过靶向ACADSB促进胃癌进展

张玉1,2,3, 顾心亮1,2,3, 李洋1,2,3, 李洵1,2,3, 黄月皎1,4, 鞠少卿2
1南通大学医学院, 南通大学, 中国南通市, 226001
2南通大学附属医院检验科, 中国南通市, 226001
3南通大学附属医院临床医学研究中心, 中国南通市, 226001
4南通大学附属医院肿瘤科, 中国南通市, 226001
摘要:胃癌(GC)是最常见的胃肠道肿瘤之一。作为一种新型的非编码RNA,转移RNA(tRNA)衍生的小RNA(tsRNA)在肿瘤中发挥着双重生物学作用。我们之前的研究揭示了tRF-23-Q99P9P9NDD作为GC诊断和预后生物标志物的潜力。在本研究中,我们首次证实了tRF-23-Q99P9P9NDD能够促进GC细胞的增殖、迁移和侵袭。双荧光素酶报告基因实验证实tRF-23-Q99P9P9NDD可以结合短/支链酰基辅酶A脱氢酶(ACADSB)的3’非编码区(UTR)位点。此外,ACADSB可以挽救tRF-23-Q99P9P9NDD对GC细胞的影响。随后,我们使用基因本体论(GO)、京都基因和基因组百科全书(KEGG)以及基因集富集分析(GSEA)发现,GC中下调的ACADSB可能通过抑制脂肪酸分解代谢和铁死亡来促进脂质积累。最后,我们在转录水平上验证了ACADSB和12个铁死亡基因之间的相关性,并通过流式细胞仪检测了活性氧(ROS)水平的变化。综上,本研究提出tRF-23-Q99P9P9NDD可能通过靶向ACADSB影响GC脂质代谢和铁死亡,从而促进GC进展。这为GC的诊断和预后监测价值提供了理论基础,并为治疗开辟了新的可能性。

关键词:tRNA衍生的小RNA(tsRNA);胃癌(GC);短/支链酰基辅酶A脱氢酶(ACADSB);分子机制;治疗;铁死亡

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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