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

作　　者：Yu ZHANG Xinliang GU Yang LI Xun LI Yuejiao HUANG Shaoqing JU 

机构地区：[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

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2024年第5期438-450,共13页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：was supported by the National Natural Science Foundation of China(Nos.82272411 and 82072363);the Jiangsu Provincial Medical Key Discipline(Laboratory)(No.ZDXK202240);the Science and Technology Project of Jiangsu Province(No.BE2023741),China。

摘　　要：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 upnew possibilities for treatment.

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

分 类 号：R735.2[医药卫生—肿瘤]