tRFs在肿瘤中的研究进展
Research Progress of tRFs in Tumor
DOI: 10.12677/ACM.2024.142583, PDF,    科研立项经费支持
作者: 白兆兆, 白鹏伟:宁夏医科大学第一临床医学院,宁夏 银川 ;王军宏:兰州大学第一临床医学院,甘肃 兰州;许 焱, 牛幸栋:甘肃中医药大学第一临床医学院,甘肃 兰州 ;达明绪*:宁夏医科大学第一临床医学院,宁夏 银川;甘肃省人民医院肿瘤外科,甘肃 兰州
关键词: tRFs生物标记物肿瘤差异表达tRFs Biomarkers Tumor Differential Expression
摘要: 转运RNA (transfer RNA, tRNA)衍生的RNA片段(transfer RNA-derived fragments, tRFs)是一种新型的小非编码RNA (non-coding RNA, ncRNA)。tRFs广泛表达于生物体的各种细胞内。研究发现tRFs可以通过调控翻译、基因表达和细胞周期对肿瘤的发生发展产生非常重要的作用,其在功能上与微小RNA (microRNA, miRNA)具有相似之处,但其具体机制尚不完全清楚,还需进一步探究。本文对tRFs的分类、生物学功能、其异常表达对不同肿瘤的影响以及在肿瘤新型诊断生物标记物和潜在治疗靶点的研究进行了综述,以期为未来的研究提供一个可能的研究思路和方向。
Abstract: RNA fragments (tRFs) derived from transporting RNA (tRNA) is a new type of small non-coding RNA (ncRNA). tRFs is widely expressed in various cells of organisms. Studies have found that tRFs can play a very important role in tumor occurrence and development by regulating translation, gene expression and cell cycle. It is functionally similar to micro-RNA (miRNA), but its specific mechanism is not completely clear and needs to be further explored. This article reviews the clas-sification and biological function of tRFs, the effect of its abnormal expression on different tumors, as well as the research on new diagnostic biomarkers and potential therapeutic targets of tumors, in order to provide a possible research idea and direction for future research.
文章引用:白兆兆, 王军宏, 白鹏伟, 许焱, 牛幸栋, 达明绪. tRFs在肿瘤中的研究进展[J]. 临床医学进展, 2024, 14(2): 4213-4220. https://doi.org/10.12677/ACM.2024.142583

参考文献

[1] Slack, F.J. (2018) Tackling Tumors with Small RNAs Derived from Transfer RNA. The New England Journal of Medi-cine, 378, 1842-1843. [Google Scholar] [CrossRef
[2] Esteller, M. (2011) Non-Coding RNAs in Human Disease. Nature Reviews Genetics, 12, 861-874. [Google Scholar] [CrossRef] [PubMed]
[3] Zhu, L., Liu, X., Pu, W., et al. (2018) tRNA-Derived Small Non-Coding RNAs in Human Disease. Cancer Letters, 419, 1-7. [Google Scholar] [CrossRef] [PubMed]
[4] Zhu, L., Ge, J., Li, T., et al. (2019) tRNA-Derived Fragments and tRNA Halves: The New Players in Cancers. Cancer Letters, 452, 31-37. [Google Scholar] [CrossRef] [PubMed]
[5] Ma, Z., Zhou, J., Shao, Y., et al. (2020) Biochemical Properties and Progress in Cancers of tRNA-Derived Fragments. Journal of Cellular Biochemistry, 121, 2058-2063. [Google Scholar] [CrossRef] [PubMed]
[6] Kumar, P., Kuscu, C. and Dutta, A. (2016) Biogenesis and Function of Transfer RNA-Related Fragments (tRFs). Trends in Biochemical Sciences, 41, 679-689. [Google Scholar] [CrossRef] [PubMed]
[7] Yu, X., Xie, Y., Zhang, S., et al. (2021) tRNA-Derived Fragments: Mechanisms Underlying Their Regulation of Gene Expression and Potential Applications as Therapeutic Targets in Cancers and Virus Infections. Theranostics, 11, 461-469. [Google Scholar] [CrossRef] [PubMed]
[8] Lee, Y.S., Shibata, Y., Malhotra, A., et al. (2009) A Novel Class of Small RNAs: tRNA-Derived RNA Fragments (tRFs). Genes & Development, 23, 2639-2649. [Google Scholar] [CrossRef] [PubMed]
[9] Qin, C., Xu, P.-P., Zhang, X., et al. (2020) Pathological Significance of tRNA-Derived Small RNAs in Neurological Disorders. Neural Regeneration Research, 15, 212-221. [Google Scholar] [CrossRef] [PubMed]
[10] Zhu, P., Yu, J. and Zhou, P. (2020) Role of tRNA-Derived Frag-ments in Cancer: Novel Diagnostic and Therapeutic Targets tRFs in Cancer. American Journal of Cancer Research, 10, 393-402.
[11] Shen, L., Tan, Z., Gan, M., et al. (2019) tRNA-Derived Small Non-Coding RNAs as Novel Epigenetic Molecules Regulating Adipogenesis. Biomolecules, 9, Article 274. [Google Scholar] [CrossRef] [PubMed]
[12] Kumar, P., Anaya, J., Mudunuri, S.B., et al. (2014) Meta-Analysis of tRNA Derived RNA Fragments Reveals That They Are Evolutionarily Conserved and Associate with AGO Proteins to Recognize Specific RNA Targets. BMC Biology, 12, Article No. 78. [Google Scholar] [CrossRef] [PubMed]
[13] Huang, B., Yang, H., Cheng, X., et al. (2017) tRF/miR-1280 Suppresses Stem Cell-Like Cells and Metastasis in Colorectal Cancer. Cancer Research, 77, 3194-3206. [Google Scholar] [CrossRef
[14] Pekarsky, Y., Balatti, V., Palamarchuk, A., et al. (2016) Dysregulation of a Family of Short Noncoding RNAs, TsRNAs, in Human Cancer. Proceedings of the National Acade-my of Sciences of the United States of America, 113, 5071-5076. [Google Scholar] [CrossRef] [PubMed]
[15] Kim, H.K., Fuchs, G., Wang, S., et al. (2017) A Trans-fer-RNA-Derived Small RNA Regulates Ribosome Biogenesis. Nature, 552, 57-62. [Google Scholar] [CrossRef] [PubMed]
[16] Sobala, A. and Hutvagner, G. (2013) Small RNAs Derived from the 5’ End of tRNA Can Inhibit Protein Translation in Human Cells. RNA Biology, 10, 553-563. [Google Scholar] [CrossRef] [PubMed]
[17] Ivanov, P., Emara, M.M., Villen, J., et al. (2011) Angiogenin-Induced tRNA Fragments Inhibit Translation Initiation. Molecular Cell, 43, 613-623. [Google Scholar] [CrossRef] [PubMed]
[18] Kuscu, C., Kumar, P., Kiran, M., et al. (2018) tRNA Fragments (tRFs) Guide Ago to Regulate Gene Expression Post- Transcriptionally in a Dicer-Independent Manner. RNA, 24, 1093-1105. [Google Scholar] [CrossRef] [PubMed]
[19] Cho, H., Lee, W., Kim, G.W., et al. (2019) Regulation of La/SSB-Dependent Viral Gene Expression by Pre-tRNA 3’ Trailer-Derived tRNA Fragments. Nucleic Acids Research, 47, 9888-9901. [Google Scholar] [CrossRef] [PubMed]
[20] Zou, L., Yang, Y., Zhou, B., et al. (2022) tRF-3013b Inhibits Gallbladder Cancer Proliferation by Targeting TPRG1L. Cellular & Molecular Biology Letters, 27, Article No. 99. [Google Scholar] [CrossRef] [PubMed]
[21] Xu, C. and Zheng, J. (2019) siRNA against TSG101 Reduces Proliferation and Induces G0/G1 Arrest in Renal Cell Carcinoma—Involvement of c-myc, cyclin E1, and CDK2. Cellular & Molecular Biology Letters, 24, Article No. 7. [Google Scholar] [CrossRef] [PubMed]
[22] Jung, Y.-S., Qian, Y. and Chen, X. (2010) Examination of the Expanding Pathways for the Regulation of P21 Expression and Activity. Cellular Signalling, 22, 1003-1012. [Google Scholar] [CrossRef] [PubMed]
[23] Capelluto, D.G.S., Kutateladze, T.G., Habas, R., et al. (2002) The DIX Domain Targets Dishevelled to Actin Stress Fibres and Vesicular Membranes. Nature, 419, 726-729. [Google Scholar] [CrossRef] [PubMed]
[24] Wu, S., Cetinkaya, C., Munoz-Alonso, M.J., et al. (2003) Myc Represses Differentiation-Induced P21CIP1 Expression via Miz-1-Dependent Interaction with the p21 Core Promoter. Oncogene, 22, 351-360. [Google Scholar] [CrossRef] [PubMed]
[25] Asghar, U., Witkiewicz, A.K., Turner, N.C., et al. (2015) The History and Future of Targeting Cyclin-Dependent Kinases in Cancer Therapy. Nature Reviews Drug Discovery, 14, 130-146. [Google Scholar] [CrossRef] [PubMed]
[26] Tadesse, S., Caldon, E.C., Tilley, W., et al. (2019) Cyclin-Dependent Kinase 2 Inhibitors in Cancer Therapy: An Update. Journal of Medicinal Chemistry, 62, 4233-4251. [Google Scholar] [CrossRef] [PubMed]
[27] Zhang, Z., Liu, Z., Zhao, W., et al. (2022) tRF-19-W4PU732S Promotes Breast Cancer Cell Malignant Activity by Targeting Inhibition of RPL27A (Ribosomal Protein-L27A). Bioengineered, 13, 2087-2098. [Google Scholar] [CrossRef] [PubMed]
[28] Falconi, M., Giangrossi, M., Zabaleta, M.E., et al. (2019) A Novel 3’-tRNA(Glu)-Derived Fragment Acts as a Tumor Suppressor in Breast Cancer by Targeting Nucleolin. The FASEB Journal, 33, 13228-13240. [Google Scholar] [CrossRef
[29] Mo, D., Jiang, P., Yang, Y., et al. (2019) A tRNA Fragment, 5’-tiRNA(Val), Suppresses the Wnt/Beta-Catenin Signaling Pathway by Targeting FZD3 in Breast Cancer. Cancer Letters, 457, 60-73. [Google Scholar] [CrossRef] [PubMed]
[30] Goodarzi, H., Liu, X., Nguyen, H.C., et al. (2015) Endogenous tRNA-Derived Fragments Suppress Breast Cancer Progression via YBX1 Displacement. Cell, 161, 790-802. [Google Scholar] [CrossRef] [PubMed]
[31] Mo, D., He, F., Zheng, J., et al. (2021) tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-Beta1/Smad3 Axis in Breast Cancer. Frontiers in Oncology, 11, Article 656078. [Google Scholar] [CrossRef] [PubMed]
[32] Sun, C., Yang, F., Zhang, Y., et al. (2018) tRNA-Derived Frag-ments as Novel Predictive Biomarkers for Trastuzumab-Resistant Breast Cancer. Cellular Physiology and Biochemistry, 49, 419-431. [Google Scholar] [CrossRef] [PubMed]
[33] Wang, J., Ma, G., Li, M., et al. (2020) Plasma tRNA Fragments Derived from 5’ Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer. Molecular Therapy Nucleic Acids, 21, 954-964. [Google Scholar] [CrossRef] [PubMed]
[34] Zhang, Y., Bi, Z., Dong, X., et al. (2021) tRNA-Derived Frag-ments: tRF-Gly-CCC-046, tRF-Tyr-GTA-010 and tRF-Pro-TGG-001 as Novel Diagnostic Biomarkers for Breast Can-cer. Thoracic Cancer, 12, 2314-2323. [Google Scholar] [CrossRef] [PubMed]
[35] Xu, W., Zhou, B., Wang, J., et al. (2021) tRNA-Derived Fragment tRF-Glu-TTC-027 Regulates the Progression of Gastric Carcinoma via MAPK Signaling Pathway. Frontiers in On-cology, 11, Article 733763. [Google Scholar] [CrossRef] [PubMed]
[36] Xu, W., Zheng, J., Wang, X., et al. (2022) tRF-Val-CAC-016 Modulates the Transduction of CACNA1d-Mediated MAPK Signaling Pathways to Suppress the Proliferation of Gastric Carcinoma. Cell Communication & Signaling, 20, Article No. 68. [Google Scholar] [CrossRef] [PubMed]
[37] Zhu, L., Li, Z., Yu, X., et al. (2021) The tRNA-Derived Frag-ment 5026a Inhibits the Proliferation of Gastric Cancer Cells by Regulating the PTEN/PI3K/AKT Signaling Pathway. Stem Cell Research & Therapy, 12, Article No. 418. [Google Scholar] [CrossRef] [PubMed]
[38] Cui, H., Li, H., Wu, H., et al. (2022) A Novel 3’tRNA-Derived Fragment tRF-Val Promotes Proliferation and Inhibits Apoptosis by Targeting EEF1A1 in Gastric Cancer. Cell Death & Disease, 13, Article No. 471. [Google Scholar] [CrossRef] [PubMed]
[39] Shen, Y., Yu, X., Ruan, Y., et al. (2021) Global Profile of tRNA-Derived Small RNAs in Gastric Cancer Patient Plasma and Identification of tRF-33-P4R8YP9LON4VDP as a New Tumor Suppressor. International Journal of Medical Sciences, 18, 1570-1579. [Google Scholar] [CrossRef] [PubMed]
[40] Shen, Y., Xie, Y., Yu, X., et al. (2021) Clinical Diagnostic Values of Transfer RNA-Derived Fragment tRF-19-3L7L73JD and Its Effects on the Growth of Gastric Cancer Cells. Journal of Cancer, 12, 3230-3238. [Google Scholar] [CrossRef] [PubMed]
[41] Lin, C., Zheng, L., Huang, R., et al. (2020) tRFs as Potential Exosome tRNA-Derived Fragment Biomarkers for Gastric Carcinoma. Clinical Laboratory, 66. [Google Scholar] [CrossRef
[42] Huang, Y., Zhang, H., Gu, X., et al. (2021) Elucidating the Role of Serum tRF-31-U5YKFN8DYDZDD as a Novel Diagnostic Biomarker in Gastric Cancer (GC). Frontiers in Oncology, 11, Article 723753. [Google Scholar] [CrossRef] [PubMed]
[43] Zheng, B., Song, X., Wang, L., et al. (2022) Plasma Exosomal tRNA-Derived Fragments as Diagnostic Biomarkers in Non-Small Cell Lung Cancer. Frontiers in Oncology, 12, Article 1037523. [Google Scholar] [CrossRef] [PubMed]
[44] You, J., Yang, G., Wu, Y., et al. (2022) Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 as Novel Diagnostic Biomarkers for Lung Adenocarcinoma. Frontiers in Oncology, 12, Article 991451. [Google Scholar] [CrossRef] [PubMed]
[45] Zhang, J., Li, L., Luo, L., et al. (2021) Screening and Potential Role of tRFs and tiRNAs Derived from tRNAs in the Carcinogenesis and Development of Lung Adenocarcinoma. Oncology Letters, 22, Article No. 506. [Google Scholar] [CrossRef] [PubMed]
[46] Shao, Y., Sun, Q., Liu, X., et al. (2017) tRF-Leu-CAG Promotes Cell Proliferation and Cell Cycle in Non-Small Cell Lung Cancer. Chemical Biology & Drug Design, 90, 730-738. [Google Scholar] [CrossRef] [PubMed]
[47] Dar, A.A., Goff, L.W., Majid, S., et al. (2010) Aurora Kinase Inhibi-tors—Rising Stars in Cancer Therapeutics? Molecular Cancer Therapeutics, 9, 268-278. [Google Scholar] [CrossRef
[48] Yang, W., Gao, K., Qian, Y., et al. (2022) A Novel tRNA-Derived Fragment AS-tDR-007333 Promotes the Malignancy of NSCLC via the HSPB1/MED29 and ELK4/MED29 Axes. Journal of Hematology & Oncology, 15, Article No. 53. [Google Scholar] [CrossRef] [PubMed]
[49] Yun, C.W., Kim, H.J., Lim, J.H., et al. (2019) Heat Shock Pro-teins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy. Cells, 9, Article 60. [Google Scholar] [CrossRef] [PubMed]
[50] Wu, J., Liu, T., Rios, Z., et al. (2017) Heat Shock Proteins and Cancer. Trends in Pharmacological Sciences, 38, 226-256. [Google Scholar] [CrossRef] [PubMed]
[51] Zhu, Z., Song, J., Guo, Y., et al. (2020) LAMB3 Promotes Tumour Progression through the AKT-FOXO3/4 Axis and Is Transcriptionally Regulated by the BRD2/Acetylated ELK4 Complex in Colorectal Cancer. Oncogene, 39, 4666-4680. [Google Scholar] [CrossRef] [PubMed]
[52] Olvedy, M., Scaravilli, M., Hoogstrate, Y., et al. (2016) A Com-prehensive Repertoire of tRNA-Derived Fragments in Prostate Cancer. Oncotarget, 7, 24766-24777. [Google Scholar] [CrossRef] [PubMed]
[53] Chiang, K.C., Tsui, K.H., Chung, L.C., et al. (2014) Cisplatin Modulates B-Cell Translocation Gene 2 to Attenuate Cell Proliferation of Prostate Carcinoma Cells in Both p53-Dependent and p53-Independent Pathways. Scientific Reports, 4, Article No. 5511. [Google Scholar] [CrossRef] [PubMed]
[54] Ramachandran, K., Gopisetty, G., Gordian, E., et al. (2009) Methyla-tion-Mediated Repression of GADD45alpha in Prostate Cancer and Its Role as a Potential Therapeutic Target. Cancer Research, 69, 1527-1535. [Google Scholar] [CrossRef
[55] Tront, J.S., Huang, Y., Fornace Jr., A.A., et al. (2010) Gadd45a Functions as a Promoter or Suppressor of Breast Cancer Dependent on the Oncogenic Stress. Cancer Research, 70, 9671-9681. [Google Scholar] [CrossRef
[56] Su, L.Y., Xin, H.Y., Liu, Y.L., et al. (2014) Anticancer Bioactive Peptide (ACBP) Inhibits Gastric Cancer Cells by Upregulating Growth Arrest and DNA Damage-Inducible Gene 45A (GADD45A). Tumor Biology, 35, 10051-10056. [Google Scholar] [CrossRef] [PubMed]
[57] Yang, C., Lee, M., Song, G., et al. (2021) tRNA(Lys)-Derived Fragment Alleviates Cisplatin-Induced Apoptosis in Prostate Cancer Cells. Pharmaceutics, 13, Article 55. [Google Scholar] [CrossRef] [PubMed]
[58] Wang, L., Liu, Y., Yan, W., et al. (2022) Clinical Significance of High Expression of tRF-Glu-TTC-2 in Prostate Carcinoma and Its Effect on Growth. American Journal of Men’s Health, 16. [Google Scholar] [CrossRef] [PubMed]
[59] Wang, Y., Xia, W., Shen, F., et al. (2022) tRNA-Derived Fragment tRF-Glu49 Inhibits Cell Proliferation, Migration and Invasion in Cervical Cancer by Targeting FGL1. On-cology Letters, 24, Article No. 334. [Google Scholar] [CrossRef] [PubMed]
[60] Li, J., Jin, L., Gao, Y., et al. (2021) Low Expression of tRF-Pro-CGG Predicts Poor Prognosis in Pancreatic Ductal Adenocarcinoma. Journal of Clinical Laboratory Analysis, 35, e23742. [Google Scholar] [CrossRef] [PubMed]
[61] Lu, X., Wu, W., Sun, D., et al. (2022) tRNA-Derived Fragment tRF-18 Facilitates Cell Proliferation and Inhibits Cell Apoptosis via Modulating KIF1B in Papillary Thyroid Carcinoma. Critical Reviews in Eukaryotic Gene Expression, 32, 21-31. [Google Scholar] [CrossRef