tsRNA在妇科疾病中的研究进展

doi:10.3870/j.issn.1672-8009.2026.01.011

摘要/Abstract

摘要： 转运RNA衍生的小RNA(tRNA-derived small RNA,tsRNA)是由前体或成熟tRNA经特异性核酸内切酶切割产生的非编码小RNA,具有多种生物学功能。在妇科疾病领域,tsRNA被证实在卵巢癌、子宫内膜癌、子宫内膜异位症等疾病中差异表达,并与疾病的发生、发展及预后密切相关。文章通过总结tsRNA在妇科疾病中的研究进展,旨在为其机制研究、早期诊断和精准治疗提供新思路。

关键词: tsRNA, 卵巢癌, 子宫内膜癌, 子宫内膜异位症, 生物标志物

Abstract: tRNA-derived small RNAs(tsRNAs)are generated from the precursor tRNA or the mature tRNA through specific enzymatic cleavage reactions and exhibit a wide range of biological functions.In the field of gynecology,tsRNAs have been demonstrated to be differentially expressed in various gynecological diseases,including ovarian cancer,endometrial cancer and endometriosis,and are closely associated with disease progression and prognosis.This review aims to summarize the progresses of current researchs on tsRNAs in gynecological disorders,with the purpose of providing new insights into their molecular mechanisms and potential applications in early diagnosis and precision medicine.

Key words: tRNA-derived small RNAs, ovarian cancer, endometrial cancer, endometriosis, biomarkers

中图分类号:

R711

何佳倍, 刘俐伶. tsRNA在妇科疾病中的研究进展[J]. 医学分子生物学杂志, 2026, 23(1): 79-84.

HE Jiabei, LIU Liling. Research Advances in tRNA-derived Small RNA in Gynecological Diseases[J]. Journal of Medical Molecular Biology, 2026, 23(1): 79-84.

参考文献

[1] ZHANG L,LIU J,HOU Y.Classification,function,and advances in tsRNA in non-neoplastic diseases[J].Cell Death Dis,2023,14(11):748.
[2] XIAO L,WANG J,JU S,et al.Disorders and roles of tsRNA,snoRNA,snRNA and PiRNA in cancer[J].J Med Genet,2022,59(7):623-631.
[3] XIE L,ZHAO Z,XIA H,et al.A novel tsRNA-5008a pr-omotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation[J].Exp Cell Res,2024,435(2):113923.
[4] XU R,DU A,DENG X,et al.tsRNA-GlyGCC promotes colorectal cancer progression and 5-FU resistance by regulating SPIB[J].J Exp Clin Cancer Res,2024,43(1):230.
[5] ZHANG J,XI Y,FEI Q,et al.Identification of tRNA-derived RNAs in adipose tissue from overweight type 2 diabetes mellitus patients and their potential biological functions[J].Front Endocrinol,2023,14:1139157.
[6] LI D,GAO X,MA X,et al.Aging-induced tRNA(Glu)-derived fragment impairs glutamate biosynthesis by targeting mitochondrial translation-dependent cristae organization[J].Cell Metab,2024,36(5):1059-1075.e9.
[7] WANG B,XIA L,ZHU D,et al.Paternal high-fat diet altered sperm 5’tsRNA-gly-GCC is associated with enhanced gluconeogenesis in the offspring[J].Front Mol Biosci,2022,9:857875.
[8] BALATTI V,NIGITA G,VENEZIANO D,et al.tsRNA si-gnatures in cancer[J].Proc Natl Acad Sci U S A,2017,114(30):8071-8076.
[9] CHEN Q,LI D,JIANG L,et al.Biological functions and clinical significance of tRNA-derived small fragment(tsRNA)in tumors:Current state and future perspectives[J].Cancer Lett,2024,587:216701.
[10] HONDA S,LOHER P,SHIGEMATSU M,et al.Sex hormone-dependent tRNA halves enhance cell proliferation in breast and prostate cancers[J].Proc Natl Acad Sci USA,2015,112(29):E3816-E3825.
[11] HONDA S,KIRINO Y.SHOT-RNAs:A novel class of tRNA-derived functional RNAs expressed in hormone-dependent cancers[J].Mol Cell Oncol,2015,3(2):e1079672.
[12] CHEN Y,SIERZPUTOWSKA-GRACZ H,GUENTHER R,et al.5-Methylcytidine is required for cooperative binding of Mg²⁺ and a conformational transition at the anticodon stem-loop of yeast phenylalanine tRNA[J].Biochemistry,1993,32(38):10249-10253.
[13] ZHANG Y,ZHANG X,SHI J,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.
[14] BLANCO S,DIETMANN S,FLORES J V,et al.Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders[J].EMBO J,2014,33(18):2020-2039.
[15] HE C,BOZLER J,JANSSEN K A,et al.TET2 chemically modifies tRNAs and regulates tRNA fragment levels[J].Nat Struct Mol Biol,2021,28(1):62-70.
[16] RASHAD S,HAN X,SATO K,et al.The stress specific impact of ALKBH1 on tRNA cleavage and tiRNA generation[J].RNA Biol,2020,17(8):1092-1103.
[17] CHEN Z,QI M,SHEN B,et al.Transfer RNA demethylase ALKBH3 promotes cancer progression via induction of tRNA-derived small RNAs[J].Nucleic Acids Res,2019,47(5):2533-2545.
[18] YING X,HU W,HUANG Y,et al.A novel tsRNA,m(7)G-3′ tiRNA Lys(TTT),promotes bladder cancer malignancy via regulating anxa2 phosphorylation[J].Adv Sci,2024,11(31):2400115.
[19] XU W,ZHOU B,WANG P,et al.N6-methyladenosine modification of 3′tRF-AlaAGC impairs PD-1 blockade efficacy by promoting lactic acid accumulation in the tumor microenvironment of gastric carcinoma[J].Drug Resist Updat,2025,79:101197.
[20] PAN Y,YAN T M,WANG J R,et al.The nature of the modification at position 37 of tRNAPhe correlates with acquired taxol resistance[J].Nucleic Acids Res,2021,49(1):38-52.
[21] ZHANG S,GU Y,GE J,et al.tRF-33-P4 R8 YP9 LON4 VDP inhibits gastric cancer progression via modulating STAT3 signaling pathway in an AGO^-₂ dependent manner[J].Oncogene,2024,43(28):2160-2171.
[22] AULAS A,FAY M M,LYONS S M,et al.Stress-specific differences in assembly and composition of stress granules and related foci[J].J Cell Sci,2017,130(5):927-937.
[23] GOODARZI H,LIU X,NGUYEN H C B,et al.Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement[J].Cell,2015,161(4):790-802.
[24] KIM H K,FUCHS G,WANG S,et al.A transfer-RNA-derived small RNA regulates ribosome biogenesis[J].Nature,2017,552(7683):57-62.
[25] SCHORN A J,GUTBROD M J,LEBLANC C,et al.LTR-retrotransposon control by tRNA-derived small RNAs[J].Cell,2017,170(1):61-71.e11.
[26] FERRO A,SACCU G,MATTIVI S,et al.Extracellular vesicles as delivery vehicles for non-coding RNAs:Potential biomarkers for chronic liver diseases[J].Biomolecules,2024,14(3):277.
[27] 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.
[28] LEE Y S,SHIBATA Y,MALHOTRA A,et al.A novel class of small RNAs:TRNA-derived RNA fragments(tRFs)[J].Genes Dev,2009,23(22):2639-2649.
[29] GUO Y,BAI D,LIU W,et al.Altered sperm tsRNAs in aged male contribute to anxiety-like behavior in offspring[J].Aging Cell,2021,20(9):e13466.
[30] WANG Q,PAN Z,LIANG S,et al.Transfer RNA-derived small RNAs(tsRNAs):A rising star in liquid biopsy[J].Genes Dis,2025,12(5):101608.
[31] SIEGEL R L,MILLER K D,FUCHS H E,et al.Cancer statistics,2022[J].CA A Cancer J Clin,2022,72(1):7-33.
[32] POKHRIYAL R,HARIPRASAD R,KUMAR L,et al.Ch-emotherapy resistance in advanced ovarian cancer patients[J].Biomark Cancer,2019,11:1179299 X19860815.
[33] CHEN B,LIU S,WANG H,et al.Differential expression profiles and function prediction of transfer RNA-derived fragments in high-grade serous ovarian cancer[J].Biomed Res Int,2021,2021:5594081.
[34] ZHANG M,LI F,WANG J,et al.tRNA-derived fragment tRF-03357 promotes cell proliferation,migration and invasion in high-grade serous ovarian cancer[J].Onco Targets Ther,2019,12:6371-6383.
[35] LIANG F,REN C,WANG J,et al.The crosstalk between STAT3 and p53/RAS signaling controls cancer cell metastasis and cisplatin resistance via the Slug/MAPK/PI3K/AKT-mediated regulation of EMT and autophagy[J].Oncogenesis,2019,8(10):59.
[36] CHEN S,LI Y,ZHI S,et al.WTAP promotes osteosarcoma tumorigenesis by repressing HMBOX1 expression in an m(6)A-dependent manner[J].Cell Death Dis,2020,11(8):659.
[37] ZHOU J,WANG M,DENG D.C-Fos/microRNA-18 a feedback loop modulates the tumor growth via HMBOX1 in human gliomas[J].Biomed Pharmacother,2018,107:1705-1711.
[38] PANOUTSOPOULOU K,MAGKOU P,DREYER T,et al.tRNA-derived small RNA 3′U-tRF(ValCAC)promotes tumour migration and early progression in ovarian cancer[J].Eur J Cancer,2023,180:134-145.
[39] PANOUTSOPOULOU K,DREYER T,DORN J,et al.tRNA(GlyGCC)-derived internal fragment(i-tRF-GlyGCC)in ovarian cancer treatment outcome and progression[J].Cancers,2021,14(1):24.
[40] CAO K Y,YAN T M,ZHANG J Z,et al.A tRNA-derived fragment from Chinese yew suppresses ovarian cancer growth via targeting TRPA1[J].Mol Ther Nucleic Acids,2022,27:718-732.
[41] SIEGEL R L,GIAQUINTO A N,JEMAL A.Cancer statistics,2024[J].CA A Cancer J Clin,2024,74(1):12-49.
[42] RIBEIRO-SANTOS P,MARTINS VIEIRA C,VIANA VE-LOSO G G,et al.Tailoring endometrial cancer treatment based on molecular pathology:Current status and possible impacts on systemic and local treatment[J].Int J Mol Sci,2024,25(14):7742.
[43] HU H,WU Y,YUAN S,et al.Identification of a novel tRNA-derived small RNA fragment,tRF-16-2 YU04 DE,with the potential of inhibiting endometrial cancer progression[J].Med Oncol,2025,42(5):173.
[44] MA J,LIU F.Study of tRNA-derived fragment tRF-20-S998LO9D in pan-cancer[J].Dis Markers,2022,2022:8799319.
[45] QIAN T,YU X,XU A,et al.tRF-20-S998LO9D inhibits endometrial carcinoma by upregulating SESN2[J].Epigenomics,2022,14(24):1563-1577.
[46] SHEN L,HONG X,ZHOU W,et al.Expression profiles of tRNA-derived fragments and their potential roles in ovarian endometriosis[J].Epigenomics,2020,12(3):183-197.
[47] LI W S,LI Y L,CAO R,et al.Differential expression and bioinformatics analysis of tRF/tiRNA in endometriosis patients[J].Biomed Res Int,2022,2022:9911472.
[48] HUANG J,CHENG J,ZHANG D,et al.Comprehensive analysis of tRNA-derived fragment expression in endometriosis using PANDORA-seq technology[J].RNA Biol,2025,22(1):1-14.
[49] LI Y,CUI S,XU Z,et al.Exosomal tRF-Leu-AAG-001 derived from mast cell as a potential non-invasive diagnostic biomarker for endometriosis[J].BMC Womens Health,2022,22(1):253.
[50] HAM J,PARK W,SONG J,et al.Fraxetin reduces endometriotic lesions through activation of ER stress,induction of mitochondria-mediated apoptosis,and generation of ROS[J].Phytomedicine,2024,123:155187.
[51] TAO E W,WANG H L,CHENG W Y,et al.A specific tRNA half,5′tiRNA-His-GTG,responds to hypoxia via the HIF1α/ANG axis and promotes colorectal cancer progression by regulating LATS2[J].J Exp Clin Cancer Res,2021,40(1):67.
[52] HUANG J,ZENG F,YI H,et al.tsRNA-3043 a intensifies apoptosis and senescence of ovarian granulosa cells to drive premature ovarian failure by targeting FLT1[J].J Mol Histol,2024,55(6):1147-1162.