Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting <italic style="font-style: italic">ACADSB</italic>

Yu ZHANG; Xinliang GU; Yang LI; Xun LI; Yuejiao HUANG; Shaoqing JU

doi:10.1631/jzus.B2300215

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

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Research Article | Updated：2024-05-09

Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB
Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB
转移RNA衍生片段tRF-23-Q99P9P9NDD通过靶向ACADSB促进胃癌进展
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 25, Issue 5, Pages: 438-450(2024)
Affiliations：

1.Medical School of Nantong University, Nantong University, Nantong 226001, China
2.Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
3.Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong 226001, China
4.Department of Medical Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China
Funds：
DOI：10.1631/jzus.B2300215
CLC：
CSTR：
Published： 15 May 2024 ，

Received： 06 April 2023 ，

Revised： 07 August 2023 ，

张玉,顾心亮,李洋等.转移RNA衍生片段tRF-23-Q99P9P9NDD通过靶向ACADSB促进胃癌进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(05):438-450.

Yu ZHANG, Xinliang GU, Yang LI, et al. Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(5):438-450(2024)
张玉,顾心亮,李洋等.转移RNA衍生片段tRF-23-Q99P9P9NDD通过靶向ACADSB促进胃癌进展[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2024,25(05):438-450. DOI： 10.1631/jzus.B2300215.

Yu ZHANG, Xinliang GU, Yang LI, et al. Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB. [J]. Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) 25(5):438-450(2024) DOI： 10.1631/jzus.B2300215.

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。

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

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.

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

Keywords

Transfer RNA (tRNA)‍-derived small RNA (tsRNA)Gastric cancer (GC)Acyl-coenzyme A dehydrogenase short/branched chain (ACADSB)Molecular mechanismTreatmentFerroptosis

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Related Institution

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The Joint Laboratory for Lung Development and Related Diseases of West China Second University Hospital, Sichuan University and School of Life Sciences of Fudan University, West China Institute of Women and Children’s Health, West China Second University Hospital, Sichuan University

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

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

DOI：10.1631/jzus.B2300215

摘要

Abstract

关键词

Keywords

references