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Volume 41 Issue 6
Jun.  2025
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Article Navigation >  Journal of Clinical Hepatology  > 2025  >  41(6): 1227-1234

Biological function of tRNA-derived small RNA and its expression and clinical significance in liver diseases

DOI: 10.12449/JCH250634
  • 1.

    Children’s Hospital，The First Affiliated Hospital of Henan University of Chinese Medicine，Zhengzhou 450000，China

  • 2.

    School of Pediatrics，Henan University of Chinese Medicine，Zhengzhou 450000，China

Research funding:

National Natural Science Foundation of China (81804142);

National Natural Science Foundation of China (82474570);

China Postdoctoral Science Foundation General Program (2023M731027)

More Information
  • Corresponding author: QIU Jianli， qiujianli@126.com （ORCID： 0000-0001-6796-3774）
  • Received Date: 2024-09-29
  • Accepted Date: 2024-11-07
  • Published Date: 2025-06-25
    Abstract
  • Liver diseases cannot be easily detected in the early stage， and although invasive diagnostic methods， such as liver biopsy， are relatively accurate， they tend to have a low degree of acceptance， which greatly limits the improvement in diagnosis and treatment techniques for liver diseases. Therefore， it is of great importance to search for new biomarkers and therapeutic targets. As an emerging biomarker for liquid biopsy， tRNA-derived small RNA （tsRNA） is abnormally expressed in various liver diseases including viral hepatitis， fatty liver disease， liver injury， and liver cancer， and it can affect the development and progression of liver diseases by regulating the biological functions such as gene expression， epigenetic regulation， and protein translation. This article reviews the origin， classification， and biological function of tsRNA， as well as the research advances in tsRNA as biomarkers and potential therapeutic targets for liver diseases， so as to provide ideas for the early diagnosis and treatment of liver diseases.

     

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  • [1]
    SARIN SK, KUMAR M, ESLAM M, et al. Liver diseases in the Asia-Pacific Region: A Lancet Gastroenterology& Hepatology Commission[J]. Lancet Gastroenterol Hepatol, 2020, 5( 2): 167- 228. DOI: 10.1016/S2468-1253(19)30342-5.
    [2]
    LIU ZQ, LIN CQ, MAO XH, et al. Changing prevalence of chronic hepatitis B virus infection in China between 1973 and 2021: A systematic literature review and meta-analysis of 3 740 studies and 231 million people[J]. Gut, 2023, 72( 12): 2354- 2363. DOI: 10.1136/gutjnl-2023-330691.
    [3]
    ZHOU JH, ZHOU F, WANG WX, et al. Epidemiological features of NAFLD from 1999 to 2018 in China[J]. Hepatology, 2020, 71( 5): 1851- 1864. DOI: 10.1002/hep.31150.
    [4]
    YANG B, ZHANG R. Progress on the treatment of metabolic associated fatty liver disease[J/CD]. Chin J Liver Dis(Electronic Edition), 2024, 16( 4): 25- 30. DOI: 10.3969/j.issn.1674-7380.2024.04.00.

    杨彬, 张瑞. 代谢相关脂肪性肝病治疗进展[J/CD]. 中国肝脏病杂志(电子版), 2024, 16( 4): 25- 30. DOI: 10.3969/j.issn.1674-7380.2024.04.00.
    [5]
    ZHANG F, JU JM, DIAO HT, et al. Innovative pharmacotherapy for hepatic metabolic and chronic inflammatory diseases in China[J]. Br J Pharmacol, 2024. DOI: 10.1111/bph.16342.[ Online ahead of print]
    [6]
    TSONEVA DK, IVANOV MN, VINCIGUERRA M. Liquid liver biopsy for disease diagnosis and prognosis[J]. J Clin Transl Hepatol, 2023, 11( 7): 1520- 1541. DOI: 10.14218/jcth.2023.00040.
    [7]
    DU J, HUANG TY, ZHENG Z, et al. Biological function and clinical application prospect of tsRNAs in digestive system biology and pathology[J]. Cell Commun Signal, 2023, 21( 1): 302. DOI: 10.1186/s12964-023-01341-8.
    [8]
    XIE YY, YAO LP, YU XC, et al. Action mechanisms and research methods of tRNA-derived small RNAs[J]. Signal Transduct Target Ther, 2020, 5( 1): 109. DOI: 10.1038/s41392-020-00217-4.
    [9]
    KATSARAKI K, ARTEMAKI PI, PAPAGEORGIOU SG, et al. Identification of a novel, internal tRNA-derived RNA fragment as a new prognostic and screening biomarker in chronic lymphocytic leukemia, using an innovative quantitative real-time PCR assay[J]. Leuk Res, 2019, 87: 106234. DOI: 10.1016/j.leukres.2019.106234.
    [10]
    PENG RF, SANTOS HJ, NOZAKI T. Transfer RNA-derived small RNAs in the pathogenesis of parasitic protozoa[J]. Genes(Basel), 2022, 13( 2): 286. DOI: 10.3390/genes13020286.
    [11]
    YU XC, XIE YY, ZHANG SS, et al. tRNA-derived fragments: Mechanisms underlying their regulation of gene expression and potential applications as therapeutic targets in cancers and virus infections[J]. Theranostics, 2021, 11( 1): 461- 469. DOI: 10.7150/thno.51963.
    [12]
    YANG N, LI RJ, LIU RA, et al. The emerging function and promise of tRNA-derived small RNAs in cancer[J]. J Cancer, 2024, 15( 6): 1642- 1656. DOI: 10.7150/jca.89219.
    [13]
    LIAO JY, GUO YH, ZHENG LL, et al. Both endo-siRNAs and tRNA-derived small RNAs are involved in the differentiation of primitive eukaryote Giardia Lamblia[J]. Proc Natl Acad Sci U S A, 2014, 111( 39): 14159- 14164. DOI: 10.1073/pnas.1414394111.
    [14]
    BALATTI V, NIGITA G, VENEZIANO D, et al. tsRNA signatures in cancer[J]. Proc Natl Acad Sci U S A, 2017, 114( 30): 8071- 8076. DOI: 10.1073/pnas.1706908114.
    [15]
    ZHANG X, HE X, LIU C, et al. IL-4 inhibits the biogenesis of an epigenetically suppressive PIWI-interacting RNA to upregulate CD1a molecules on monocytes/dendritic cells[J]. J Immunol, 2016, 196( 4): 1591- 1603. DOI: 10.4049/jimmunol.1500805.
    [16]
    TONG LH, ZHANG WX, QU BC, et al. The tRNA-derived fragment-3017A promotes metastasis by inhibiting NELL2 in human gastric cancer[J]. Front Oncol, 2021, 10: 570916. DOI: 10.3389/fonc.2020.570916.
    [17]
    ZHANG SS, GU YQ, GE JX, et al. tRF-33-P4R8YP9LON4VDP inhibits gastric cancer progression via modulating STAT3 signaling pathway in an AGO2-dependent manner[J]. Oncogene, 2024, 43( 28): 2160- 2171. DOI: 10.1038/s41388-024-03062-9.
    [18]
    GOODARZI H, LIU XH, NGUYEN HCB, et al. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement[J]. Cell, 2015, 161( 4): 790- 802. DOI: 10.1016/j.cell.2015.02.053.
    [19]
    FALCONI M, GIANGROSSI M, ZABALETA ME, et al. A novel 3'- tRNAGlu-derived fragment acts as a tumor suppressor in breast cancer by targeting nucleolin[J]. FASEB J, 2019, 33( 12): 13228- 13240. DOI: 10.1096/fj.201900382rr.
    [20]
    CHEN Q, YAN MH, CAO ZH, et al. Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder[J]. Science, 2016, 351( 6271): 397- 400. DOI: 10.1126/science.aad7977.
    [21]
    SARKER G, SUN WF, ROSENKRANZ D, et al. Maternal overnutrition programs hedonic and metabolic phenotypes across generations through sperm tsRNAs[J]. Proc Natl Acad Sci USA, 2019, 116( 21): 10547- 10556. DOI: 10.1073/pnas.1820810116.
    [22]
    ZHANG YF, ZHANG XD, SHI JC, et al. Dnmt2 mediates intergenerational transmission of paternally acquired metabolic disorders through sperm small non-coding RNAs[J]. Nat Cell Biol, 2018, 20( 5): 535- 540. DOI: 10.1038/s41556-018-0087-2.
    [23]
    YU T, XIE YM, TANG C, et al. Dnmt2-null sperm block maternal transmission of a paramutant phenotype[J]. Biol Reprod, 2021, 105( 3): 603- 612. DOI: 10.1093/biolre/ioab086.
    [24]
    SHI JC, ZHANG YF, ZHOU T, et al. tsRNAs: The Swiss army knife for translational regulation[J]. Trends Biochem Sci, 2019, 44( 3): 185- 189. DOI: 10.1016/j.tibs.2018.09.007.
    [25]
    WU CD, LIU DK, ZHANG LF, et al. 5'-tiRNA-Gln inhibits hepatocellular carcinoma progression by repressing translation through the interaction with eukaryotic initiation factor 4A-I[J]. Front Med, 2023, 17( 3): 476- 492. DOI: 10.1007/s11684-022-0966-6.
    [26]
    GEBETSBERGER J, WYSS L, MLECZKO AM, et al. A tRNA-derived fragment competes with mRNA for ribosome binding and regulates translation during stress[J]. RNA Biol, 2017, 14( 10): 1364- 1373. DOI: 10.1080/15476286.2016.1257470.
    [27]
    MLECZKO AM, CELICHOWSKI P, BĄKOWSKA-ŻYWICKA K. Transfer RNA-derived fragments target and regulate ribosome-associated aminoacyl-transfer RNA synthetases[J]. Biochim Biophys Acta Gene Regul Mech, 2018: S1874-9399(17)30380- 2. DOI: 10.1016/j.bbagrm.2018.06.001.
    [28]
    FRICKER R, BROGLI R, LUIDALEPP H, et al. A tRNA half modulates translation as stress response in Trypanosoma brucei[J]. Nat Commun, 2019, 10( 1): 118. DOI: 10.1038/s41467-018-07949-6.
    [29]
    KIM HK, XU JP, CHU K, et al. A tRNA-derived small RNA regulates ribosomal protein S28 protein levels after translation initiation in humans and mice[J]. Cell Rep, 2019, 29( 12): 3816- 3824. DOI: 10.1016/j.celrep.2019.11.062.
    [30]
    SAIKIA M, JOBAVA R, PARISIEN M, et al. Angiogenin-cleaved tRNA halves interact with cytochrome c, protecting cells from apoptosis during osmotic stress[J]. Mol Cell Biol, 2014, 34( 13): 2450- 2463. DOI: 10.1128/MCB.00136-14.
    [31]
    KEAM SP, SOBALA A, HAVE S TEN, et al. tRNA-derived RNA fragments associate with human multisynthetase complex(MSC) and modulate ribosomal protein translation[J]. J Proteome Res, 2017, 16( 2): 413- 420. DOI: 10.1021/acs.jproteome.6b00267.
    [32]
    DI FAZIO A, GULLEROVA M. An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology[J]. Br J Cancer, 2023, 128( 9): 1625- 1635. DOI: 10.1038/s41416-023-02191-4.
    [33]
    BRAICU C, ZIMTA AA, HARANGUS A, et al. The function of non-coding RNAs in lung cancer tumorigenesis[J]. Cancers(Basel), 2019, 11( 5): 605. DOI: 10.3390/cancers11050605.
    [34]
    SHI JC, ZHANG YF, TAN DM, et al. PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications[J]. Nat Cell Biol, 2021, 23( 4): 424- 436. DOI: 10.1038/s41556-021-00652-7.
    [35]
    RUZMAN L, MIKOLASEVIC I, BARABA DEKANIC K, et al. Advances in diagnosis of chronic liver diseases in pediatric patients[J]. World J Pediatr, 2018, 14( 6): 541- 547. DOI: 10.1007/s12519-018-0197-8.
    [36]
    SINGH S, OSNA NA, KHARBANDA KK. Treatment options for alcoholic and non-alcoholic fatty liver disease: A review[J]. World J Gastroenterol, 2017, 23( 36): 6549- 6570. DOI: 10.3748/wjg.v23.i36.6549.
    [37]
    ZHANG PY, WANG WY, MAO M, et al. Similarities and differences: A comparative review of the molecular mechanisms and effectors of NAFLD and AFLD[J]. Front Physiol, 2021, 12: 710285. DOI: 10.3389/fphys.2021.710285.
    [38]
    ZHONG FD, HU ZG, JIANG KQ, et al. Complement C3 activation regulates the production of tRNA-derived fragments Gly-tRFs and promotes alcohol-induced liver injury and steatosis[J]. Cell Res, 2019, 29( 7): 548- 561. DOI: 10.1038/s41422-019-0175-2.
    [39]
    HUANG P, TU B, LIAO HJ, et al. Elevation of plasma tRNA fragments as a promising biomarker for liver fibrosis in nonalcoholic fatty liver disease[J]. Sci Rep, 2021, 11( 1): 5886. DOI: 10.1038/s41598-021-85421-0.
    [40]
    KIM Y, LEE DH, PARK SH, et al. The interplay of microRNAs and transcription factors in autophagy regulation in nonalcoholic fatty liver disease[J]. Exp Mol Med, 2021, 53( 4): 548- 559. DOI: 10.1038/s12276-021-00611-0.
    [41]
    ZHU JJ, CHENG ML, ZHAO XK. A tRNA-derived fragment(tRF-3001b) aggravates the development of nonalcoholic fatty liver disease by inhibiting autophagy[J]. Life Sci, 2020, 257: 118125. DOI: 10.1016/j.lfs.2020.118125.
    [42]
    ZHU JJ, WEN Y, ZHANG QL, et al. The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway[J]. J Transl Med, 2022, 20( 1): 128. DOI: 10.1186/s12967-022-03343-5.
    [43]
    ANWANWAN D, SINGH SK, SINGH S, et al. Challenges in liver cancer and possible treatment approaches[J]. Biochim Biophys Acta Rev Cancer, 2020, 1873( 1): 188314. DOI: 10.1016/j.bbcan.2019.188314.
    [44]
    ZUO Y, CHEN SQ, YAN LL, et al. Development of a tRNA-derived small RNA diagnostic and prognostic signature in liver cancer[J]. Genes Dis, 2021, 9( 2): 393- 400. DOI: 10.1016/j.gendis.2021.01.006.
    [45]
    ZHU L, LI J, GONG YL, et al. Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis[J]. Mol Cancer, 2019, 18( 1): 74. DOI: 10.1186/s12943-019-1000-8.
    [46]
    WANG Y, WENG QY, GE JX, et al. tRNA-derived small RNAs: Mechanisms and potential roles in cancers[J]. Genes Dis, 2022, 9( 6): 1431- 1442. DOI: 10.1016/j.gendis.2021.12.009.
    [47]
    ZHAN SB, YANG P, ZHOU SK, et al. Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis[J]. Front Med, 2022, 16( 2): 216- 226. DOI: 10.1007/s11684-022-0920-7.
    [48]
    XU TX, YUAN J, SONG F, et al. Exploring the functional role of tRF-39-8HM2OSRNLNKSEKH9 in hepatocellular carcinoma[J]. Heliyon, 2024, 10( 5): e27153. DOI: 10.1016/j.heliyon.2024.e27153.
    [49]
    ZHOU YQ, HU JJ, LIU L, et al. Gly-tRF enhances LCSC-like properties and promotes HCC cells migration by targeting NDFIP2[J]. Cancer Cell Int, 2021, 21( 1): 502. DOI: 10.1186/s12935-021-02102-8.
    [50]
    KIM HK, FUCHS G, WANG SC, et al. A transfer-RNA-derived small RNA regulates ribosome biogenesis[J]. Nature, 2017, 552( 7683): 57- 62. DOI: 10.1038/nature25005.
    [51]
    LUO JJ, LI JQ, LI P, et al. Acute-on-chronic liver failure: Far to go-a review[J]. Crit Care, 2023, 27( 1): 259. DOI: 10.1186/s13054-023-04540-4.
    [52]
    XU WL, YU MX, WU YK, et al. Plasma-derived exosomal sncRNA as a promising diagnostic biomarker for early detection of HBV-related acute-on-chronic liver failure[J]. Front Cell Infect Microbiol, 2022, 12: 923300. DOI: 10.3389/fcimb.2022.923300.
    [53]
    YING SY, LI PC, WANG JQ, et al. tRF-Gln-CTG-026 ameliorates liver injury by alleviating global protein synthesis[J]. Signal Transduct Target Ther, 2023, 8( 1): 144. DOI: 10.1038/s41392-023-01351-5.
    [54]
    SELITSKY SR, BARAN-GALE J, HONDA M, et al. Small tRNA-derived RNAs are increased and more abundant than microRNAs in chronic hepatitis B and C[J]. Sci Rep, 2015, 5: 7675. DOI: 10.1038/srep07675.
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