Emerging roles of tRNA-derived fragments in cancer

Fu, Min; Gu, Jianmei; Wang, Maoye; Zhang, Jiahui; Chen, Yanke; Jiang, Pengcheng; Zhu, Taofeng; Zhang, Xu

doi:10.1186/s12943-023-01739-5

Molecular Cancer

Table 1 The deregulated tRFs in cancer

From: Emerging roles of tRNA-derived fragments in cancer

Cancer type	Expression level	tRF	Sample type	Clinical significance	Ref
Breast cancer	Upregulated	SHOT-RNAs	Tissue	SHOT-RNAs are more enriched in ER⁺ BC tissues than triple-negative BC and normal breast tissues	[33]
		tRF-19-W4PU732S	Tissue	High level expression predicts poor survival	[104]
		tRF-34-RKVP4P9L5FZUHM	Tissue	High expression correlates with poor survival of BC patients	[105]
		nlr-18-949M9Y0Q, nlr-20-D6PUMZQZ	Tissue	Higher levels of both tRFs predict poorer OS; In the T cell exhaustion group, low level of nlr-18-949M9Y0Q predicts better OS	[106]
		tRF-32-XSXMSL73VL4YK	Tissue	No obvious correlation	[107]
		nlr-31-W01KN44VD3YZE	Tissue	Not mentioned	[108]
		nlr-30-W01KN44VD3YZ, nlr-32-FKSZZ6KSNNQ7Q, tRF-34-PUDP4PZKFJ7PEP	Plasma	High expression of nlr-30-W01KN44VD3YZ and tRF-34-PUDP4PZKFJ7PEP predict worse DFS and OS	[98]
		tRF-32-PS5P4PW3FJHP1	Serum, Ev from serum	High diagnostic accuracy for BC is obtained in a model with miR-21-5p (3’ addition C) and miR-23a-3p	[109]
	Downregulated	tRF-17-SMKVNM1, tRF-20-6NMH490V, and tRF-20-VIPZK0JN	Tissue	tRF levels decrease in metastatic samples compared to primary tumors	[42]
		nlr-14-7O58FX, nlr-21-F0L9XZ30E, nlr-34-5QKDN6QQ1362HQ	Tissue	Higher level of each tRF predicts improved OS; In the T cell exhaustion group, high level of nlr-34-5QKDN6QQ1362HQ predicts improved survival	[106]
		tRF-32-Q99P9P9NH57SJ, tRF-17-79MP9PP	Tissue, serum	Lower expression correlates with higher stage progression and lymph node metastasis	[107, 110, 111]
		tRF-18-YRRHQFD2, tRF-18-HSQSD2D2, tRF-20-B2NZW7O6	Tissue, serum	Expression levels are also downregulated in early-stage BC patients	[112]
		tDR-000620	Serum	Low tDR-000620 expression is an independent adverse predictive factor for recurrence-free survival of triple-negative BC	[113]
		nlr-21-F5W8E7OME, tRF-18-18VBY9DV, tRF-23-NB57BK87DZ	Serum	Expression levels are downregulated in non-triple-negative BC	[114]
		tRF-32-1HPSR9O9337KF	Plasma	tRF-32-1HPSR9O9337KF levels significantly decrease in the blood of patients with HER2⁺ BC reflecting tumor status (control > early cancer > metastatic cancer)	[115]
		tRF-18-HR0VX6D2, iso-26-QO608YX91ZE	Plasma	They are better biomarker candidates than their corresponding miRNAs	[116]
		tRF-16-87R8WPE, tRF-22-PNR8YP9LL, tRF-23-PNR8YP9LD6, tRF-16-SP5830D, tRF-24-OB1690PQIY, tRF-28-OB1690PQR304	Plasma, exosomes from plasma and tissues	Low expressed tRF-16-87R8WPE of HER2⁺ early BC patients correlates to worse DFS and OS	[8]
Gastric Cancer	Upregulated	tRF-19-FRJ4O1E2	Tissue	Higher tRF-19-FRJ4O1E2 correlates with higher lymph node metastasis	[117]
		tRF-18-8R1546D2	Tissue	tRF-18-8R1546D2 can discriminate GC stage I-II and III-IV, lymph node metastasis and differentiation	[118]
		nlr-18-08P2F5DF	Tissue	Expression is positively correlated with tumor size and the depth of tumor invasion	[119]
		tRF-29-RRJ89O9NF5JP	Tissue, serum	Expression is positively correlated with the degree of lymph node metastasis and tumor grade	[120]
		tRF-23-Q99P9P9NDD	Tissue, serum	Expression is positively associated with T stage, lymph node metastasis, TNM stage, and nerve/vascular invasion	[121]
		tRF-31-U5YKFN8DYDZDD	Serum	Expression is positively associated with depth of invasion, lymph node metastasis, TNM stage, and vascular invasion	[122]
	Downregulated	nlr-15-D47RMZ,nlr-17-XI61Z7Q	Tissue	Lower expression correlates with larger tumor size and poorer differentiation	[123, 124]
		tRF-24-V29K9UV3IU, tRF-34-Q99P9P9NH57S15	Tissue	Not mentioned	[125–127]
		tRF-34-86V8WPMN1E8Y2Q	Tissue, plasma	Lower expression correlates with larger tumor size	[128]
		tRF-18-79MP9P04	Tissue, plasma	Lower expression correlates with larger tumor size, TNM stage, lymph node metastasis and poorer survival	[99]
		tRF-33-P4R8YP9LON4VDP	Plasma	Not mentioned	[101]
		tRF-19-3L7L73JD	Plasma	Higher expression predicts smaller tumor size	[129]
Colorectal cancer	Upregulated	nlr-26-LIKFW7X7JNE	Tissue	nlr-26-LIKFW7X7JNE is upregulated in both colon adenomas and adenocarcinomas	[73]
		tRF-phe-GAA-031, tRF-VAL-TCA-002	Tissue	Increased expression positively correlates with distant metastasis and clinical stage, and predicts poorer survival	[130]
		tRF-32-6978WPRLXN48Q	Tissue	High tRF-32-6978WPRLXN48Q level predicts poor DFS, OS, and high recurrence	[131]
		tRF-35-PW5SVP9N15WV7W	Tissue	Expression correlates positively with tumor size, but not with age, sex, or clinical stage	[12]
		tRF-34-Q99P9P9NH57S15, tRF-30-ROD8N0X0JYOY, tRF-29-R9J89O9NF5JP, tRF-18-8R1546D2	Tissue	Not mentioned	[132, 133]
		tRF-33-79MP9P9NH57SD3	Tissue, serum	Increased expression is positively associated with lymph node and distant metastasis	[134]
		tRF-35-PNR8YP9LON4VN1	Plasma	Increased expression positively correlates with pathological stage and metastasis	[135]
	Upregulated/downregulated	tRF-18-HSRVK7D2, tRF-33-PSQP4PW3FJI0W, tRF-33-PSQP4PW3FJIKW, tRF-32-O7M8LOMLQHWU3, tRF-18-H9Q867D2, tRF-16-I3FJQSD	Tissue	They are included in a six-tRF-based prognostic model with high risk score predicting worse survival, especially for stage III patients	[133]
	Downregulated	tRF-16-79MP9PE, tRF-16-RP9830D, tRF-16-RPM830E, tRF-22-WB86Q3P92, tRF-22-WE8SPOX52, tRF-22-WE8S68L52, nlr-17-863IP5J	Tissue	Not mentioned	[132, 133, 136]
Lung cancer	Upregulated	nlr-15-395P4P	Tissue	High expression is associated with postoperative recurrence and poor prognosis	[137]
		nlr-34-4P5830MMUKLYHE	Tissue, serum	nlr-34-4P5830MMUKLYHE is greatly upregulated in stage III and stage IV cases, and increases with stage progression	[138]
		nlr-28-PNR8YP9LONDQ	Tissue, plasma	High nlr-28-PNR8YP9LONDQ predicts poor survival of NSCLC	[139]
		tRF-21-RK9P4P9L0, tRF-16-PSQP4PE	Tissue, serum	tRF-21-RKP4P9L0 is negatively associated with prognosis in lung adenocarcinoma	[140]
		tRF-31-79MP9P9NH57SD	Serum	Expression is positively associated with clinical stage and the malignancy of lymph node	[141]
		tRF-30-RK9P4P9L5HMV, tRF-31-RK9P4P9L5HMVE, tRF-26-MI7O3B1NR8E, tRF-27-WJ9X0UD394N, tRF-26-SP5830MMUKD, tRF-29-MIF91SS2P4IR, tRF-30-3JVIJMRPFQRD, tRF-31-ROD8N0X0JYOYE, tRF-32-ROD8N0X0JYOYO	Peripheral blood mononuclear cells	TRY-RNA signature precisely discriminates between control, lung cancer, and pulmonary tuberculosis subjects	[142]
	Downregulated	nlr-29-P9MWYRKHNZI2, iso-25-QO608YX91Z, nlr-33-Z4ODD8U82KP90Q, nlr-31-SU12RXXNBZY3E	Tissue	Not mentioned	[65, 73]
		tRF-16-L85J3KE	Tissue, serum	No significant correlation with prognosis is observed	[140]
		AS-tDR-007872	Tissue, plasma	AS-tDR-007872 is more sensitive in distinguishing stage III and IV than stage I-II NSCLC patients	[143]
Leukemia	Upregulated	tRF-21-ZPEK45H5D	Peripheral blood mononuclear cells	Overexpression of tRF-21-ZPEK45H5D is related to poor OS of the CLL patients	[144]
	Downregulated	i-tRF of tRNA^GlyCCC	Peripheral blood mononuclear cells	Reduced OS for CLL patients with positive expression of this i-tRF	[145]
		nlr-29-P9MWYRKHNZI2, iso-25-QO608YX91Z, nlr-33-Z4ODD8U82KP90Q, nlr-31-SU12RXXNBZY3E	Peripheral blood mononuclear cells	Not mentioned	[65, 73]
		tDR-Asp family	Bone marrow	Decreased tDR-Asp can predict myelodysplastic syndromes that are likely to progress to acute myeloid leukemia	[146]
	NOT significant	tRF-18-5J3KYU05, tRF-18-HR0VX6D2	Peripheral blood mononuclear cells	High expression levels are associated with inferior OS	[147, 148]
Pancreatic cancer	Upregulated	AS-tDR-000064, AS-tDR-000069, AS-tDR-000102	Tissue	Not mentioned	[149]
		tRF-18-HR0VX6D2	Tissue	Not mentioned	[150]
		tRF-30-6978WPRLXN4V, tRF-18-HRERXFD2	Tissue, serum	The tRF-30-6978WPRLXN4V-high and/or tRF-18-HRERXFD2-high PC patients show significantly worse prognosis	[151]
		tRF-41-N5EX62Z6EXEY0VWUD, tRF-37-KSBE78YLKZKWE52, tRF-23-YOY9Q867D2	Tissue, serum	High tRF-41-N5EX62Z6EXEY0VWUD expression is associated with advanced tumor stage and liver metastasis, and predict poor OS	[152]
	Downregulated	AS-tDR-001391	Tissue	Not mentioned	[149]
		nlr-33-OJ5B8LK7F1BUDV	Tissue	Low expression is associated with advanced TNM stage, N stage and predicts poor survival	[153]
		tRF-21-VBY9PYKHD	Tissue	Patients with low expression levels have poor prognosis	[154]
Liver cancer	Upregulated	tRF-30-PNR8YP9LON4V	Tissue	High expression predicts poor survival	[155]
Liver cancer	Upregulated	tRF-40-EFOK8YR951K36D26, tRF-34-QNR8VP94FQFY1Q, tRF-32-79MP9P9NH57SJ, tRF-31-87R8WP9N1EWJ0	Plasma exosomes	Not mentioned	[156]
Ovarian cancer	Upregulated	nlr-24-5D0RKRKNFQ, nlr-25-756BIW7K5Z	Tissue	Not mentioned	[73]
		tRF-32-P4R8YP9LON4V3, tRF-25-9NJ4S2I7L7	Serum	Not mentioned	[157]
		i-tRFs of tRNA^GlyGCC	Tissue, serum	Increased expression is associated with advanced stages, suboptimal debulking and early progression, and predicts poor OS of early ovarian cancer	[158]
		tRF-03357, tRF-03358	Serum	Expression level is significantly increased in high-grade serous ovarian cancer	[159]
	Downregulated	tRF-28-PNR8YO9LOND5, tRF-28-PNR8YP9LOND5	Serum	Not mentioned	[157]
Prostate cancer	Upregulated	SHOT-RNAs	Tissue	SHOT-RNAs are upregulated in AR⁺ prostate cancer	[33]
Bladder cancer	Upregulated	tRF-34-Q99P9P9NH57S15, tRF-32-P4R8YP9LON4V3, tRF-31-P4R8YP9LON4VD	Tissue	Not mentioned	[160]
	Upregulated	tRF-29-PSQP4PW3FJF4	Tissue, serum	Increased expression is associated with aggressive tumor phenotype, early disease progression and poor treatment outcome	[161]
	Downregulated	tRF- + 1:T20-Ser-TGA-1	Tissue	Not mentioned	[160]
Renal cancer	Downregulated	5’ halves of tRNA^ValAAC	Tissue	Expression level is inversely correlated with staging and grading	[162]
Renal cancer	Downregulated	5’ halves of tRNA^ArgCCT, tRNA^GluCTC,and tRNA^LysTTT	Tissue, serum	Lower expression levels are associated with adverse clinicopathological parameters	[163]
Esophageal squamous cell cancer	Upregulated	tRNA-GlyGCC-5	Salivary exosomes	Patients with high risk score have shorter OS and progression-free survival, and benefit more from adjuvant therapy	[164]
Multiple myeloma	Upregulated	tRF-34-86J8WPMN1E8Y2Q	Tissue	Not mentioned	[165]
	Upregulated	tRF-18-5J3KYU05, tRF-18-HR0VX6D2	CD138 + plasma cells	The OS and PFS are significantly longer in MM patients with high tRF-18-5J3KYU05 or tRF-18-HR0VX6D2 levels	[166]
	Downregulated	tRF-17-8YQ84V2	Tissue	Not mentioned	[165]
	Unkown	tRF-60:77-Thr-TGT-1,tRF-22-PY5P4PZ3H	Tissue	tRF-60:77-Thr-TGT-1 is upregulated and tRF-22-PY5P4PZ3H is downregulated in relapsed/refractory MM compared with newly diagnosed MM	[103]
Cervical cancer	Upregulated	tRF-22-ZRS3S3RX5	Tissue	Expression is positively associated with the gastric subtype of endocervical adenocarcinoma	[167]
Papillary thyroid cancer	Upregulated	tRF-32-PNR8YP9LON4V3, tRF-39-0VL8K87SIRMM12E2	Tissue	Not mentioned	[168, 169]
Lymphoma	Downregulated	tRF-22-WE8SPOX52	Tissue	Not mentioned	[170]
Pharyngeal cancer	Upregulated	tRF-30-PSQP4PW3FJIK	Tissue	Increased expression closely relates to tumor staging, differentiation grade, smoking history and drinking history, and predicts metastasis	[100]
	Upregulated	tRF-28-Q99P9P9NH50E, tRF-24-QW58309N0Y	Tissue	Not mentioned	[171]
	Downregulated	tRF-22-WD8YQ84V2	Tissue	Not mentioned	[171]
Laryngeal cancer	Downregulated	tRF-33-Q1Q89P9L842205	Tissue	Low expression is closely associated with lymph node metastasis and advanced stages	[172]
Head and neck squamous cell carcinoma	Upregulated	tRF-20-S998LO9D	Tissue	High expression level is significantly associated with poor OS	[173]
Head and neck squamous cell carcinoma	Upregulated in tissue Downregulated in serum	5’ tRNA-Val-CAC-2–1 half	Tissue, serum	Not mentioned	[174]
Uveal melanoma	Downregulated	tRF-22-BP4MJYSZH, tRF-21-45DBNIB9B	Tissue	Low expression relates to various molecular phenotypes, metastatic disease, and poor patient survival	[175]
Glioma	Downregulated	nlr-20-2IHZI73Z, tRF-18-HRE9XFD2, and tRF-22-WB86N7O52	Tissue	High expression correlates with positive IDH mutant and better survival	[176]
Cholangiocarcinoma	Upregulated	tRF-20-LE2WMK81	Tissue	Not mentioned	[177]
Cholangiocarcinoma	Downregulated	tRF-34-JJ6RRNLIK898HR, tRF-38-0668K87SERM492V, tRF-39-0668K87SERM492E2	Tissue	Not mentioned	[177]

The names of tRFs are converted to the standardized license plate notation as possible [21]
Abbreviations: SHOT-RNAs Sex HOrmone-dependent TRNA-derived RNAs, ER Estrogen receptor, BC Breast cancer, OS Overall survival, DFS Disease-free survival, EV Extracellular vesicles, GC Gastric cancer, NSCLC Non-small cell lung cancer, CLL Chronic lymphocytic leukemia, PC Pancreatic cancer, AR Androgen receptor; MM Multiple myeloma

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ISSN: 1476-4598

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