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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
纸质出版日期: 2024-05-15 ,
收稿日期: 2023-04-06 ,
修回日期: 2023-08-07 ,
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
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
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。
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.
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
Transfer RNA (tRNA)-derived small RNA (tsRNA)Gastric cancer (GC)Acyl-coenzyme A dehydrogenase short/branched chain (ACADSB)Molecular mechanismTreatmentFerroptosis
Carracedo A, Cantley LC, Pandolfi PP, 2013. Cancer metabolism: fatty acid oxidation in the limelight. Nat Rev Cancer, 13(4):227-232. https://doi.org/10.1038/nrc3483https://doi.org/10.1038/nrc3483
Correa P, 2013. Gastric cancer: overview. Gastroenterol Clin North Am, 42(2):211-217. https://doi.org/10.1016/j.gtc.2013.01.002https://doi.org/10.1016/j.gtc.2013.01.002
di Fazio A, Gullerova M, 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. https://doi.org/10.1038/s41416-023-02191-4https://doi.org/10.1038/s41416-023-02191-4
Ericksen RE, Lim SL, Mcdonnell E, 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. https://doi.org/10.1016/j.cmet.2018.12.020https://doi.org/10.1016/j.cmet.2018.12.020
Falconi M, Giangrossi M, Zabaleta ME, 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. https://doi.org/10.1096/fj.201900382RRhttps://doi.org/10.1096/fj.201900382RR
Han Y, Peng YH, Liu SS, 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. https://doi.org/10.1186/s13046-021-02190-4https://doi.org/10.1186/s13046-021-02190-4
Haussecker D, Huang Y, Lau A, et al., 2010. Human tRNA-derived small RNAs in the global regulation of RNA silencing. RNA, 16(4):673-695. https://doi.org/10.1261/rna.2000810https://doi.org/10.1261/rna.2000810
Hsieh LC, Lin SI, Shih ACC, et al., 2009. Uncovering small RNA-mediated responses to phosphate deficiency in Arabidopsis by deep sequencing. Plant Physiol, 151(4):2120-2132. https://doi.org/10.1104/pp.109.147280https://doi.org/10.1104/pp.109.147280
Huang BQ, Yang HP, Cheng XX, et al., 2017. tRF/miR-1280 suppresses stem cell-like cells and metastasis in colorectal cancer. Cancer Res, 77(12):3194-3206. https://doi.org/10.1158/0008-5472.Can-16-3146https://doi.org/10.1158/0008-5472.Can-16-3146
Kim HK, Fuchs G, Wang SC, et al., 2017. A transfer-RNA-derived small RNA regulates ribosome biogenesis. Nature, 552(7683):57-62. https://doi.org/10.1038/nature25005https://doi.org/10.1038/nature25005
Kumar P, Kuscu C, Dutta A, 2016. Biogenesis and function of transfer RNA-related fragments (tRFs). Trends Biochem Sci, 41(8):679-689. https://doi.org/10.1016/j.tibs.2016.05.004https://doi.org/10.1016/j.tibs.2016.05.004
Lai SW, Kuo YH, Liao KF, 2020. Statin therapy and gastric cancer death. Postgrad Med J, 96(1133):178. https://doi.org/10.1136/postgradmedj-2019-136994https://doi.org/10.1136/postgradmedj-2019-136994
Li J, Zhu L, Cheng J, et al., 2021. Transfer RNA-derived small RNA: a rising star in oncology. Semin Cancer Biol, 75:29-37. https://doi.org/10.1016/j.semcancer.2021.05.024https://doi.org/10.1016/j.semcancer.2021.05.024
Li XZ, Liu XY, Zhao DZ, et al., 2021. tRNA-derived small RNAs: novel regulators of cancer hallmarks and targets of clinical application. Cell Death Discov, 7:249. https://doi.org/10.1038/s41420-021-00647-1https://doi.org/10.1038/s41420-021-00647-1
Liu BW, Cao JL, Wang XY, et al., 2021. Deciphering the tRNA-derived small RNAs: origin, development, and future. Cell Death Dis, 13:24. https://doi.org/10.1038/s41419-021-04472-3https://doi.org/10.1038/s41419-021-04472-3
Liu XH, Zhang WY, Wang HR, et al., 2022. Decreased expression of ACADSB predicts poor prognosis in clear cell renal cell carcinoma. Front Oncol, 11:762629. https://doi.org/10.3389/fonc.2021.762629https://doi.org/10.3389/fonc.2021.762629
Lu D, Yang ZY, Xia QY, et al., 2020. ACADSB regulates ferroptosis and affects the migration, invasion, and proliferation of colorectal cancer cells. Cell Biol Int, 44(11):2334-2343. https://doi.org/10.1002/cbin.11443https://doi.org/10.1002/cbin.11443
Luan N, Mu YL, Mu JY, et al., 2021. Dicer1 promotes colon cancer cell invasion and migration through modulation of tRF-20-MEJB5Y13 expression under hypoxia. Front Genet, 12:638244. https://doi.org/10.3389/fgene.2021.638244https://doi.org/10.3389/fgene.2021.638244
Park EJ, Kim TH, 2018. Fine-tuning of gene expression by tRNA-derived fragments during abiotic stress signal transduction. Int J Mol Sci, 19(2):518. https://doi.org/10.3390/ijms19020518https://doi.org/10.3390/ijms19020518
Qu L, He XY, Tang Q, et al., 2022. Iron metabolism, ferroptosis, and lncRNA in cancer: knowns and unknowns. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 23(10):844-862. https://doi.org/10.1631/jzus.B2200194https://doi.org/10.1631/jzus.B2200194
Qu YY, Zhao R, Zhang HL, 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. https://doi.org/10.1158/0008-5472.Can-19-1023https://doi.org/10.1158/0008-5472.Can-19-1023
Rozen R, Vockley J, Zhou LB, 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. https://doi.org/10.1006/geno.1994.1617https://doi.org/10.1006/geno.1994.1617
Shen L, Shan YS, Hu HM, et al., 2013. Management of gastric cancer in Asia: resource-stratified guidelines. Lancet Oncol, 14(12):e535-e547. https://doi.org/10.1016/s1470-2045(13)70436-4https://doi.org/10.1016/s1470-2045(13)70436-4
Stockwell BR, Angeli JPF, Bayir H, et al., 2017. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell, 171(2):273-285. https://doi.org/10.1016/j.cell.2017.09.021https://doi.org/10.1016/j.cell.2017.09.021
Sung H, Ferlay J, Siegel RL, 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. https://doi.org/10.3322/caac.21660https://doi.org/10.3322/caac.21660
Tao EW, Cheng WY, Li WL, 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. https://doi.org/10.1002/jcp.29057https://doi.org/10.1002/jcp.29057
Torres AG, Reina O, Stephan-Otto Attolini C, 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. https://doi.org/10.1073/pnas.1821120116https://doi.org/10.1073/pnas.1821120116
Wen JT, Huang ZH, Li QH, et al., 2021. Research progress on the tsRNA classification, function, and application in gynecological malignant tumors. Cell Death Discov, 7:388. https://doi.org/10.1038/s41420-021-00789-2https://doi.org/10.1038/s41420-021-00789-2
Xu DD, Qiao DQ, Lei YL, et al., 2022. Transfer RNA-derived small RNAs (tsRNAs): versatile regulators in cancer. Cancer Lett, 546:215842. https://doi.org/10.1016/j.canlet.2022.215842https://doi.org/10.1016/j.canlet.2022.215842
Yang M, Mo YZ, Ren DX, et al., 2023. Transfer RNA-derived small RNAs in tumor microenvironment. Mol Cancer, 22:32. https://doi.org/10.1186/s12943-023-01742-whttps://doi.org/10.1186/s12943-023-01742-w
Zhang Y, Gu XL, Qin XY, et al., 2022. Evaluation of serum tRF-23-Q99P9P9NDD as a potential biomarker for the clinical diagnosis of gastric cancer. Mol Med, 28:63. https://doi.org/10.1186/s10020-022-00491-8https://doi.org/10.1186/s10020-022-00491-8
Zhou K, Diebel KW, Holy J, et al., 2017. A tRNA fragment, tRF5-Glu, regulates BCAR3 expression and proliferation in ovarian cancer cells. Oncotarget, 8(56):95377-95391. https://doi.org/10.18632/oncotarget.20709https://doi.org/10.18632/oncotarget.20709
Zhou N, Bao JK, 2020. FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database, 2020:baaa021. https://doi.org/10.1093/database/baaa021https://doi.org/10.1093/database/baaa021
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