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Current Genomics

Editor-in-Chief

ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

Research Article

Identification of tRNA-Derived Fragments Expression Profile in Breast Cancer Tissues

Author(s): Xiaoming Wang, Yining Yang, Xuyan Tan, Xuelian Mao, Da Wei, Yufeng Yao, Pan Jiang, Dongping Mo, Ting Wang and Feng Yan*

Volume 20, Issue 3, 2019

Page: [199 - 213] Pages: 15

DOI: 10.2174/1389202920666190326145459

Abstract

Background: In recent years, tRFs(transfer RNA-Derived Fragments) and transfer RNADerived Stress-induced RNAs (or tRNA halves) have been shown to have vital roles in cancer biology. We aimed to reveal the expression profile of tRNA-derived fragments in breast cancer tissues in the study, and to explore their potential as biomarkers of breast cancer.

Methods: We characterized the tRNA-derived fragments expression profile from 6 paired clinical breast cancer tissues and adjacent normal samples. Then we selected 6 significantly expressed tRNAderived fragments and screened the genes for validation by using Quantitative Real-time PCR. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes biological pathway were finally analyzed.

Results: We found 30 differentially expressed tRNA-derived fragments across our dataset, out of which 17 were up-regulated, and 13 were down-regulated. Compared with 16 clinical breast cancer tissues and adjacent normal tissues by qPCR, the results demonstrated that tRF-32-Q99P9P9NH57SJ (FC = -2.6476, p = 0.0189), tRF-17-79MP9PP (FC = -4.8984, p = 0.0276) and tRF-32- XSXMSL73VL4YK (FC = 6.5781, p = 0.0226) were significantly expressed in breast cancer tissues (p < 0.001). tRF-32-XSXMSL73VL4YK was significantly up-regulated, and tRF-32- Q99P9P9NH57SJ and tRF-17-79MP9PP were significantly down-regulated in which the expression patterns were similar to the sequencing results. The top ten significant results of GO and KEGG pathways enrichment analysis were presented.

Conclusion: Our studies have demonstrated that there were significantly expressed tRNA-derived fragments in breast cancer tissues. They are hopefully to become biomarkers and would be valuable researches in this area.

Keywords: Breast cancer, tRNA-derived fragments, expression profile, biomarker, genomes, gene ontology.

Graphical Abstract
[1]
Miller, K.D.; Siegel, R.L.; Lin, C.C.; Mariotto, A.B.; Kramer, J.L.; Rowland, J.H.; Stein, K.D.; Alteri, R.; Jemal, A. Cancer treatment and survivorship statistics, 2016. CA Cancer J. Clin., 2016, 66(4), 271-289.
[2]
Zeng, H.; Chen, W.; Zheng, R.; Zhang, S.; Ji, J.S.; Zou, X.; Xia, C.; Sun, K.; Yang, Z.; Li, H.; Wang, N.; Han, R.; Liu, S.; Li, H.; Mu, H.; He, Y.; Xu, Y.; Fu, Z.; Zhou, Y.; Jiang, J.; Yang, Y.; Chen, J.; Wei, K.; Fan, D.; Wang, J.; Fu, F.; Zhao, D.; Song, G.; Chen, J.; Jiang, C.; Zhou, X.; Gu, X.; Jin, F.; Li, Q.; Li, Y.; Wu, T.; Yan, C.; Dong, J.; Hua, Z.; Baade, P.; Bray, F.; Jemal, A.; Yu, X.Q.; He, J. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries. Lancet Glob. Health, 2018, 6(5), e555-e567.
[3]
Wu, X.; Zeng, R.; Wu, S.; Zhong, J.; Yang, L.; Xu, J. Comprehensive expression analysis of miRNA in breast cancer at the miRNA and isomiR levels. Gene, 2015, 557(2), 195-200.
[4]
Hamam, R.; Hamam, D.; Alsaleh, K.A.; Kassem, M.; Zaher, W.; Alfayez, M.; Aldahmash, A.; Alajez, N.M. Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers. Cell Death Dis., 2017, 8(9), e3045.
[5]
Zhou, J.; Liu, S.; Chen, Y.; Fu, Y.; Silver, A.J.; Hill, M.S.; Lee, I.; Lee, Y.S.; Bao, X. Identification of two novel functional tRNA-derived fragments induced in response to respiratory syncytial virus infection. J. Gen. Virol., 2017, 98(7), 1600-1610.
[6]
Magee, R.G.; Telonis, A.G.; Loher, P.; Londin, E.; Rigoutsos, I. Profiles of miRNA isoforms and tRNA fragments in prostate cancer. Sci. Rep., 2018, 8(1), 5314.
[7]
Pekarsky, Y.; Balatti, V.; Palamarchuk, A.; Rizzotto, L.; Veneziano, D.; Nigita, G.; Rassenti, L.Z.; Pass, H.I.; Kipps, T.J.; Liu, C.G.; Croce, C.M. Dysregulation of a family of short noncoding RNAs, tsRNAs, in human cancer. Proc. Natl. Acad. Sci. USA, 2016, 113(18), 5071-5076.
[8]
Honda, S.; Kirino, Y. SHOT-RNAs: A novel class of tRNA-derived functional RNAs expressed in hormone-dependent cancers. Mol. Cell. Oncol., 2016, 3(2), e1079672.
[9]
Blanco, S.; Dietmann, S.; Flores, J.V.; Hussain, S.; Kutter, C.; Humphreys, P.; Lukk, M.; Lombard, P.; Treps, L.; Popis, M.; Kellner, S.; Holter, S.M.; Garrett, L.; Wurst, W.; Becker, L.; Klopstock, T.; Fuchs, H.; Gailus-Durner, V.; Hrabe de Angelis, M.; Karadottir, R.T.; Helm, M.; Ule, J.; Gleeson, J.G.; Odom, D.T.; Frye, M. Aberrant methylation of tRNAs links cellular stress to neuro-developmental disorders. EMBO J., 2014, 33(18), 2020-2039.
[10]
Venkatesh, T.; Suresh, P.S.; Tsutsumi, R. tRFs: miRNAs in disguise. Gene, 2016, 579(2), 133-138.
[11]
Shen, Y.; Yu, X.; Zhu, L.; Li, T.; Yan, Z.; Guo, J. Transfer RNA-derived fragments and tRNA halves: biogenesis, biological functions and their roles in diseases. J. Mol. Med., 2018, 96(11), 1167-1176.
[12]
Green, D.; Fraser, W.D.; Dalmay, T. Transfer RNA-derived small RNAs in the cancer transcriptome. Pflugers Arch., 2016, 468(6), 1041-1047.
[13]
Sun, C.; Fu, Z.; Wang, S.; Li, J.; Li, Y.; Zhang, Y.; Yang, F.; Chu, J.; Wu, H.; Huang, X.; Li, W.; Yin, Y. Roles of tRNA-derived fragments in human cancers. Cancer Lett., 2018, 414, 16-25.
[14]
Saikia, M.; Hatzoglou, M. The many virtues of tRNA-derived stress-induced RNAs (tiRNAs): discovering novel mechanisms of stress response and effect on human health. J. Biol. Chem., 2015, 290(50), 29761-29768.
[15]
Telonis, A.G.; Loher, P.; Honda, S.; Jing, Y.; Palazzo, J.; Kirino, Y.; Rigoutsos, I. Dissecting tRNA-derived fragment complexities using personalized transcriptomes reveals novel fragment classes and unexpected dependencies. Oncotarget, 2015, 6(28), 24797-24822.
[16]
Keam, S.P.; Hutvagner, G. tRNA-derived Fragments (tRFs): emerging new roles for an ancient RNA in the regulation of gene expression. Life (Basel), 2015, 5(4), 1638-1651.
[17]
Kumar, P.; Mudunuri, S.B.; Anaya, J.; Dutta, A. tRFdb: a database for transfer RNA fragments. Nucleic Acids Res., 2015, 43, D141-D145.
[18]
Hoogstrate, Y.; Jenster, G.; Martens-Uzunova, E.S. FlaiMapper: computational annotation of small ncRNA-derived fragments using RNA-seq high-throughput data. Bioinformatics (Oxford, England), 2015, 31(5), 665-673.
[19]
Pliatsika, V.; Loher, P.; Magee, R.; Telonis, A.G.; Londin, E.; Shigematsu, M.; Kirino, Y.; Rigoutsos, I. MINTbase v2.0: a comprehensive database for tRNA-derived fragments that includes nuclear and mitochondrial fragments from all The Cancer Genome Atlas projects. Nucleic Acids Res., 2018, 46, D152-D159.
[20]
Loher, P.; Telonis, A.G.; Rigoutsos, I. MINTmap: fast and exhaustive profiling of nuclear and mitochondrial tRNA fragments from short RNA-seq data. Sci. Rep., 2017, 7, 41184.
[21]
Lee, Y.S.; Shibata, Y.; Malhotra, A.; Dutta, A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev., 2009, 23(22), 2639-2649.
[22]
Zheng, L.L.; Xu, W.L.; Liu, S.; Sun, W.J.; Li, J.H.; Wu, J.; Yang, J.H.; Qu, L.H. tRF2Cancer: a web server to detect tRNA-derived small RNA fragments (tRFs) and their expression in multiple cancers. Nucleic Acids Res., 2016, 44(W1), W185-W193.
[23]
Goodarzi, H.; Liu, X.; Nguyen, H.C.; Zhang, S.; Fish, L.; Tavazoie, S.F. Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell, 2015, 161(4), 790-802.
[24]
Sobala, A.; Hutvagner, G. Small RNAs derived from the 5′ end of tRNA can inhibit protein translation in human cells. RNA Biol., 2013, 10(4), 553-563.
[25]
Olvedy, M.; Scaravilli, M.; Hoogstrate, Y.; Visakorpi, T.; Jenster, G.; Martens-Uzunova, E.S. A comprehensive repertoire of tRNA-derived fragments in prostate cancer. Oncotarget, 2016, 7(17), 24766-24777.
[26]
Ebhardt, H.A.; Tsang, H.H.; Dai, D.C.; Liu, Y.; Bostan, B.; Fahlman, R.P. Meta-analysis of small RNA-sequencing errors reveals ubiquitous post-transcriptional RNA modifications. Nucleic Acids Res., 2009, 37(8), 2461-2470.
[27]
Magee, R.; Telonis, A.G.; Cherlin, T.; Rigoutsos, I.; Londin, E. Assessment of isomiR discrimination using commercial qPCR methods. Noncoding RNA, 2017, 3(2), 1-12.
[28]
Dhahbi, J.M.; Spindler, S.R.; Atamna, H.; Boffelli, D.; Martin, D.I. Deep sequencing of serum small RNAs identifies patterns of 5′ tRNA half and YRNA fragment expression associated with breast cancer. Biomark. Cancer, 2014, 6, 37-47.
[29]
Telonis, A.G.; Rigoutsos, I. Race disparities in the contribution of miRNA isoforms and tRNA-derived fragments to triple-negative breast cancer. Cancer Res., 2018, 78, 1140-1154.
[30]
Cui, Y.; Huang, Y.; Wu, X.; Zheng, M.; Xia, Y.; Fu, Z.; Ge, H.; Wang, S.; Xie, H. Hypoxia-induced tRNA-derived fragments, novel regulatory factor for doxorubicin resistance in triple-negative breast cancer. J. Cell. Physiol., 2019, 234(6), 8740-8751.
[31]
Balatti, V.; Nigita, G.; Veneziano, D.; Drusco, A.; Stein, G.S.; Messier, T.L.; Farina, N.H.; Lian, J.B.; Tomasello, L.; Liu, C.G.; Palamarchuk, A.; Hart, J.R.; Bell, C.; Carosi, M.; Pescarmona, E.; Perracchio, L.; Diodoro, M.; Russo, A.; Antenucci, A.; Visca, P.; Ciardi, A.; Harris, C.C.; Vogt, P.K.; Pekarsky, Y.; Croce, C.M. tsRNA signatures in cancer. Proc. Natl. Acad. Sci. USA, 2017, 114(30), 8071-8076.
[32]
Soares, A.R.; Santos, M. Discovery and function of transfer RNA-derived fragments and their role in disease. Wiley Interdiscip. Rev. RNA, 2017, 8(6), e1423.
[33]
Cech, T.R.; Steitz, J.A. The noncoding RNA revolution-trashing old rules to forge new ones. Cell, 2014, 157(1), 77-94.
[34]
Keam, S.P.; Sobala, A.; Ten Have, S.; Hutvagner, G. tRNA-derived rna fragments associate with human Multisynthetase Complex (MSC) and modulate ribosomal protein translation. J. Proteome Res., 2017, 16(2), 413-420.
[35]
Li, Q.; Hu, B.; Hu, G.W.; Chen, C.Y.; Niu, X.; Liu, J.; Zhou, S.M.; Zhang, C.Q.; Wang, Y.; Deng, Z.F. tRNA-derived small non-coding RNAs in response to ischemia inhibit angiogenesis. Sci. Rep., 2016, 6, 20850.
[36]
Zhao, C.; Tolkach, Y.; Schmidt, D.; Kristiansen, G.; Muller, S.C.; Ellinger, J. 5′-tRNA halves are dysregulated in clear cell renal cell carcinoma. J. Urol., 2018, 199(2), 378-383.
[37]
Nientiedt, M.; Deng, M.; Schmidt, D.; Perner, S.; Muller, S.C.; Ellinger, J. Identification of aberrant tRNA-halves expression patterns in clear cell renal cell carcinoma. Sci. Rep., 2016, 6, 37158.

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