Abstract
tsRNAs are small noncoding RNAs that originate from tRNA cleavage and play important regulatory roles in gene expression, translation, transcription, and epigenetic modification. The dysregulation of tsRNAs in cancer disrupts gene expression and perturbs various cellular activities, including cell proliferation, apoptosis, migration, and invasion. Moreover, tsRNAs may influence cancer development by regulating related cell signaling pathways. In this review, we first examine the origins and classification of tsRNAs and their effects on tumor cell activity. To highlight the latest research progress of tsRNAs and signaling pathways, we summarize the possible mechanisms of tsRNAs in specific tumor-related signaling pathways, including the Wnt, TGFb1, MAPK, PI3K-AKT, Notch, and MDM2/p53 signaling pathways, that have been identified in recent research.
Graphical Abstract
[http://dx.doi.org/10.1136/jmedgenet-2021-108327] [PMID: 35145038]
[http://dx.doi.org/10.3390/genes9050246] [PMID: 29748504]
[http://dx.doi.org/10.1016/j.tibs.2021.05.001] [PMID: 34053843]
[http://dx.doi.org/10.3390/ncrna5010018] [PMID: 30781726]
[PMID: 31656062]
[http://dx.doi.org/10.1016/j.semcancer.2021.05.024] [PMID: 34029740]
[http://dx.doi.org/10.21037/tlcr-21-829] [PMID: 34858784]
[http://dx.doi.org/10.1172/JCI148130] [PMID: 34779408]
[http://dx.doi.org/10.2147/OTT.S320176] [PMID: 34285510]
[http://dx.doi.org/10.3389/fonc.2021.679366] [PMID: 34055648]
[http://dx.doi.org/10.3389/fonc.2021.723753] [PMID: 34497770]
[http://dx.doi.org/10.1186/s11658-022-00354-4] [PMID: 35922753]
[http://dx.doi.org/10.2147/OTT.S161109] [PMID: 29695914]
[http://dx.doi.org/10.1016/j.critrevonc.2015.12.005] [PMID: 26775730]
[http://dx.doi.org/10.3390/ijms14011179] [PMID: 23303278]
[http://dx.doi.org/10.1002/cam4.1105] [PMID: 29047224]
[http://dx.doi.org/10.1002/jcp.30276] [PMID: 33580511]
[http://dx.doi.org/10.3389/fonc.2021.656078] [PMID: 33912465]
[http://dx.doi.org/10.1016/j.canlet.2019.05.007] [PMID: 31078732]
[http://dx.doi.org/10.1038/s41420-021-00647-1] [PMID: 34537813]
[http://dx.doi.org/10.1080/15476286.2021.1922009] [PMID: 33998370]
[http://dx.doi.org/10.1016/j.canlet.2019.03.012] [PMID: 30905816]
[http://dx.doi.org/10.3390/ncrna3010002] [PMID: 29657274]
[PMID: 32195016]
[http://dx.doi.org/10.1038/s41420-021-00789-2] [PMID: 34907180]
[http://dx.doi.org/10.1261/rna.066126.118] [PMID: 29844106]
[http://dx.doi.org/10.1007/s00018-020-03720-7] [PMID: 33388834]
[http://dx.doi.org/10.7150/jca.46055] [PMID: 33193887]
[http://dx.doi.org/10.5808/GI.2015.13.4.94] [PMID: 26865839]
[http://dx.doi.org/10.1261/rna.2000810] [PMID: 20181738]
[http://dx.doi.org/10.1016/j.bbadis.2021.166314] [PMID: 34863896]
[http://dx.doi.org/10.1111/cbdd.12994] [PMID: 28378898]
[http://dx.doi.org/10.1186/s13045-022-01270-y] [PMID: 35526007]
[http://dx.doi.org/10.1155/2022/3475955] [PMID: 35756407]
[http://dx.doi.org/10.1186/s12935-022-02481-6] [PMID: 35115004]
[http://dx.doi.org/10.1038/s41419-022-04930-6] [PMID: 35585048]
[http://dx.doi.org/10.3389/fonc.2020.570916] [PMID: 33665159]
[http://dx.doi.org/10.1016/j.abb.2020.108467] [PMID: 32592804]
[http://dx.doi.org/10.1186/s12964-022-00857-9] [PMID: 35590368]
[http://dx.doi.org/10.3389/fonc.2021.733763] [PMID: 34497772]
[http://dx.doi.org/10.7150/ijms.53220] [PMID: 33746573]
[http://dx.doi.org/10.2147/OTT.S266130] [PMID: 33149609]
[http://dx.doi.org/10.2147/CMAR.S363629] [PMID: 35958946]
[http://dx.doi.org/10.7150/jca.51567] [PMID: 33976732]
[http://dx.doi.org/10.1186/s13287-021-02497-1] [PMID: 34294122]
[http://dx.doi.org/10.1186/s12935-021-02102-8] [PMID: 34537070]
[http://dx.doi.org/10.1111/cas.15505] [PMID: 35879647]
[http://dx.doi.org/10.1080/21655979.2022.2064206] [PMID: 35442152]
[http://dx.doi.org/10.1158/0008-5472.CAN-16-3146] [PMID: 28446464]
[http://dx.doi.org/10.1186/s13046-021-02190-4] [PMID: 35065674]
[PMID: 33527013]
[http://dx.doi.org/10.1186/s13046-021-01836-7] [PMID: 33588913]
[http://dx.doi.org/10.2147/OTT.S206861] [PMID: 31496739]
[http://dx.doi.org/10.3390/pharmaceutics13010055] [PMID: 33406670]
[http://dx.doi.org/10.3390/cancers14194555] [PMID: 36230476]
[http://dx.doi.org/10.1093/carcin/bgab058] [PMID: 34216208]
[http://dx.doi.org/10.1080/21655979.2021.2023796] [PMID: 35030975]
[http://dx.doi.org/10.1002/jcp.29419] [PMID: 31919859]
[http://dx.doi.org/10.1096/fj.201900382RR] [PMID: 31560576]
[http://dx.doi.org/10.1186/s13046-021-02024-3] [PMID: 34225773]
[http://dx.doi.org/10.3892/ol.2022.13232] [PMID: 35251343]
[http://dx.doi.org/10.1080/21655979.2021.1955177] [PMID: 34323647]
[http://dx.doi.org/10.21037/atm-21-6240] [PMID: 35284538]
[http://dx.doi.org/10.3109/08977194.2012.752737] [PMID: 23256519]
[http://dx.doi.org/10.1007/s12017-021-08700-z] [PMID: 35067780]
[http://dx.doi.org/10.1242/dev.146589] [PMID: 29884654]
[http://dx.doi.org/10.1101/gad.1424006] [PMID: 16751178]
[http://dx.doi.org/10.4149/neo_2022_220206N138] [PMID: 35293765]
[http://dx.doi.org/10.1186/s12935-022-02538-6] [PMID: 35292013]
[http://dx.doi.org/10.7150/jca.62652] [PMID: 35281864]
[http://dx.doi.org/10.1038/s41388-022-02259-0] [PMID: 35277657]
[http://dx.doi.org/10.1155/2022/2174758] [PMID: 35251169]
[http://dx.doi.org/10.1080/21655979.2022.2036917] [PMID: 35246020]
[http://dx.doi.org/10.18632/aging.203911] [PMID: 35200157]
[http://dx.doi.org/10.1038/nature05674] [PMID: 17377531]
[http://dx.doi.org/10.1007/s12026-022-09267-y] [PMID: 35147920]
[http://dx.doi.org/10.1155/2014/141747] [PMID: 24891760]
[http://dx.doi.org/10.1016/j.apsb.2018.01.008] [PMID: 30109180]
[http://dx.doi.org/10.1016/j.bbrc.2022.03.039] [PMID: 35299072]
[http://dx.doi.org/10.1016/j.jep.2022.115167] [PMID: 35271947]
[http://dx.doi.org/10.1080/15384101.2021.2023305] [PMID: 35258413]
[http://dx.doi.org/10.1007/s11033-021-06607-3] [PMID: 34357550]
[PMID: 30535469]
[http://dx.doi.org/10.1002/cne.23580] [PMID: 24610700]
[http://dx.doi.org/10.1159/000513070] [PMID: 33596588]
[http://dx.doi.org/10.2174/22123970MTEzaODMD4] [PMID: 33530915]
[http://dx.doi.org/10.1002/jcp.27262] [PMID: 30192008]
[http://dx.doi.org/10.1002/dneu.20506] [PMID: 17638387]
[http://dx.doi.org/10.1016/j.biopha.2020.110484] [PMID: 32768966]
[http://dx.doi.org/10.1016/j.semcancer.2019.05.012] [PMID: 31128298]
[http://dx.doi.org/10.1016/j.lfs.2020.118513] [PMID: 33011222]
[http://dx.doi.org/10.2741/4443] [PMID: 27100493]
[http://dx.doi.org/10.1007/s40265-020-01394-w] [PMID: 32894420]
[http://dx.doi.org/10.3892/mmr.2018.8769] [PMID: 29568883]
[http://dx.doi.org/10.1007/s12029-017-0024-9] [PMID: 29110225]
[PMID: 27115169]
[http://dx.doi.org/10.1007/s00011-021-01442-5] [PMID: 33558976]
[http://dx.doi.org/10.1146/annurev-biophys-101920-082204] [PMID: 33534608]
[http://dx.doi.org/10.1016/j.anireprosci.2017.03.017] [PMID: 28400072]
[http://dx.doi.org/10.1007/s13402-022-00663-y] [PMID: 35357654]
[http://dx.doi.org/10.1016/j.cellsig.2022.110268] [PMID: 35143930]
[http://dx.doi.org/10.7150/jca.61385] [PMID: 35069900]
[http://dx.doi.org/10.1080/21655979.2021.2023983] [PMID: 35030977]
[http://dx.doi.org/10.1007/s12032-017-1039-6] [PMID: 28918490]
[http://dx.doi.org/10.1016/0092-8674(91)90111-B] [PMID: 1831692]
[http://dx.doi.org/10.1016/j.bbcan.2021.188556] [PMID: 33932560]
[http://dx.doi.org/10.1093/jmcb/mjz060] [PMID: 31282934]
[http://dx.doi.org/10.1093/jmcb/mjz026] [PMID: 30925588]
[http://dx.doi.org/10.3390/ijms21218387] [PMID: 33182266]
[http://dx.doi.org/10.1146/annurev-pathol-012414-040349] [PMID: 27022975]
[http://dx.doi.org/10.1158/0008-5472.CAN-14-1446] [PMID: 25477334]
[http://dx.doi.org/10.1101/cshperspect.a026062] [PMID: 27141080]
[PMID: 23585010]
[http://dx.doi.org/10.1016/j.molmet.2019.10.002] [PMID: 31685430]
[http://dx.doi.org/10.1007/s10120-021-01187-4] [PMID: 33864161]
[PMID: 28975980]
[http://dx.doi.org/10.1007/s10456-020-09707-z] [PMID: 32020421]
[http://dx.doi.org/10.3892/mmr.2020.11725] [PMID: 33236135]
[http://dx.doi.org/10.1002/jcp.26816] [PMID: 30069972]
[http://dx.doi.org/10.3892/mmr.2021.12091] [PMID: 33880579]
[http://dx.doi.org/10.1093/nar/27.1.29] [PMID: 9847135]
[http://dx.doi.org/10.1371/journal.pone.0184129] [PMID: 28873455]
[http://dx.doi.org/10.3389/fmolb.2021.780621] [PMID: 34988117]
[http://dx.doi.org/10.3390/cancers12082230] [PMID: 32785169]
[http://dx.doi.org/10.1155/2022/2646173] [PMID: 35035608]
[http://dx.doi.org/10.1002/jcp.29185] [PMID: 31535382]
[http://dx.doi.org/10.3390/biomedicines9121811] [PMID: 34944627]
[http://dx.doi.org/10.2147/OTT.S302594] [PMID: 33911877]
[http://dx.doi.org/10.1016/j.omtn.2020.07.026] [PMID: 32814252]
[http://dx.doi.org/10.3892/or.2019.7178] [PMID: 31173257]
[http://dx.doi.org/10.1186/s12859-021-04167-8] [PMID: 33971811]
[http://dx.doi.org/10.3892/ol.2019.10601] [PMID: 31452788]
[http://dx.doi.org/10.1089/cmb.2019.0305] [PMID: 32392430]
[http://dx.doi.org/10.1016/j.omtn.2021.07.013] [PMID: 34513311]
[http://dx.doi.org/10.1016/j.molimm.2021.08.015] [PMID: 34464838]
[http://dx.doi.org/10.3389/fcell.2021.707572] [PMID: 34447751]
[http://dx.doi.org/10.1111/jcmm.15858] [PMID: 32939933]
[http://dx.doi.org/10.1186/s13287-020-01882-6] [PMID: 32831139]
[http://dx.doi.org/10.1016/j.bbrc.2019.09.009] [PMID: 31629473]