Full Text:   <730>

Summary:  <212>

Suppl. Mater.: 

CLC number: 

On-line Access: 2024-05-10

Received: 2023-04-06

Revision Accepted: 2023-08-07

Crosschecked: 2024-05-10

Cited: 0

Clicked: 923

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

-   Go to

Article info.
Open peer comments

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


Share this article to: More <<< Previous Article|

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.

@article{title="Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB",
author="Yu ZHANG, Xinliang GU, Yang LI, Xun LI, Yuejiao HUANG, Shaoqing JU",
journal="Journal of Zhejiang University Science B",
volume="25",
number="5",
pages="438-450",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300215"
}

%0 Journal Article
%T Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB
%A Yu ZHANG
%A Xinliang GU
%A Yang LI
%A Xun LI
%A Yuejiao HUANG
%A Shaoqing JU
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 5
%P 438-450
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300215

TY - JOUR
T1 - Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB
A1 - Yu ZHANG
A1 - Xinliang GU
A1 - Yang LI
A1 - Xun LI
A1 - Yuejiao HUANG
A1 - Shaoqing JU
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 5
SP - 438
EP - 450
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300215


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

Reference

[1]CarracedoA, CantleyLC, PandolfiPP, 2013. Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer, 13(4):227-232.

[2]CorreaP, 2013. Gastric cancer: overview. Gastroenterol Clin North Am, 42(2):211-217.

[3]di FazioA, GullerovaM, 2023. An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology. Br J Cancer, 128(9):1625-1635.

[4]EricksenRE, LimSL, McdonnellE, et al., 2019. Loss of BCAA catabolism during carcinogenesis enhances mTORC1 activity and promotes tumor development and progression. Cell Metab, 29(5):1151-1165.e6.

[5]FalconiM, GiangrossiM, ZabaletaME, et al., 2019. A novel 3'-tRNAGlu-derived fragment acts as a tumor suppressor in breast cancer by targeting nucleolin. FASEB J, 33(12):13228-13240.

[6]HanY, PengYH, LiuSS, et al., 2022. tRF3008A suppresses the progression and metastasis of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner. J Exp Clin Cancer Res, 41:32.

[7]HausseckerD, HuangY, LauA, et al., 2010. Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA, 16(4):673-695.

[8]HsiehLC, LinSI, ShihACC, et al., 2009. Uncovering small RNA-mediated responses to phosphate deficiency in Arabidopsis by deep sequencing. Plant Physiol, 151(4):2120-2132.

[9]HuangBQ, YangHP, ChengXX, et al., 2017. tRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer. Cancer Res, 77(12):3194-3206.

[10]KimHK, FuchsG, WangSC, et al., 2017. A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature, 552(7683):57-62.

[11]KumarP, KuscuC, DuttaA, 2016. Biogenesis and function of transfer RNA-related fragments (tRFs). Trends Biochem Sci, 41(8):679-689.

[12]LaiSW, KuoYH, LiaoKF, 2020. Statin therapy and gastric cancer death. Postgrad Med J, 96(1133):178.

[13]LiJ, ZhuL, ChengJ, et al., 2021. Transfer RNA-derived small RNA: a rising star in oncology. Semin Cancer Biol, 75:29-37.

[14]LiXZ, LiuXY, ZhaoDZ, et al., 2021. tRNA-derived small RNAs: novel regulators of cancer hallmarks and targets of clinical application. Cell Death Discov, 7:249.

[15]LiuBW, CaoJL, WangXY, et al., 2021. Deciphering the tRNA-derived small RNAs: origin, development, and future. Cell Death Dis, 13:24.

[16]LiuXH, ZhangWY, WangHR, et al., 2022. Decreased expression of ACADSB predicts poor prognosis in clear cell renal cell carcinoma. Front Oncol, 11:762629.

[17]LuD, YangZY, XiaQY, et al., 2020. ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells. Cell Biol Int, 44(11):2334-2343.

[18]LuanN, MuYL, MuJY, et al., 2021. Dicer1 promotes colon cancer cell invasion and migration through modulation of tRF-20-MEJB5Y13 expression under hypoxia. Front Genet, 12:638244.

[19]ParkEJ, KimTH, 2018. Fine-tuning of gene expression by tRNA-derived fragments during abiotic stress signal transduction. Int J Mol Sci, 19(2):518.

[20]QuL, HeXY, TangQ, et al., 2022. Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(10):844-862.

[21]QuYY, ZhaoR, ZhangHL, et al., 2020. Inactivation of the AMPK-GATA3-ECHS1 pathway induces fatty acid synthesis that promotes clear cell renal cell carcinoma growth. Cancer Res, 80(2):319-333.

[22]RozenR, VockleyJ, ZhouLB, et al., 1994. Isolation and expression of a cDNA encoding the precursor for a novel member (ACADSB) of the acyl-CoA dehydrogenase gene family. Genomics, 24(2):280-287.

[23]ShenL, ShanYS, HuHM, et al., 2013. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol, 14(12):e535-e547.

[24]StockwellBR, AngeliJPF, BayirH, et al., 2017. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell, 171(2):273-285.

[25]SungH, FerlayJ, SiegelRL, et al., 2021. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 71(3):209-249.

[26]TaoEW, ChengWY, LiWL, et al., 2020. tiRNAs: a novel class of small noncoding RNAs that helps cells respond to stressors and plays roles in cancer progression. J Cell Physiol, 235(2):683-690.

[27]TorresAG, ReinaO, Stephan-Otto AttoliniC, et al., 2019. Differential expression of human tRNA genes drives the abundance of tRNA-derived fragments. Proc Natl Acad Sci USA, 116(17):8451-8456.

[28]WenJT, HuangZH, LiQH, et al., 2021. Research progress on the tsRNA classification, function, and application in gynecological malignant tumors. Cell Death Discov, 7:388.

[29]XuDD, QiaoDQ, LeiYL, et al., 2022. Transfer RNA-derived small RNAs (tsRNAs): versatile regulators in cancer. Cancer Lett, 546:215842.

[30]YangM, MoYZ, RenDX, et al., 2023. Transfer RNA-derived small RNAs in tumor microenvironment. Mol Cancer, 22:32.

[31]ZhangY, GuXL, QinXY, et al., 2022. Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer. Mol Med, 28:63.

[32]ZhouK, DiebelKW, HolyJ, et al., 2017. A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells. Oncotarget, 8(56):95377-95391.

[33]ZhouN, BaoJK, 2020. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database, 2020:baaa021.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE