tsRNA作为肿瘤诊断和预后标志物的研究进展

Advances in the study of tsRNA as diagnostic and prognostic biomarkers in cancer

转运RNA(transfer RNA,tRNA)可结合相应的氨基酸,并将其运送到核糖体上,促进蛋白质的翻译。tRNA衍生的小RNA(transfer RNA-derived small RNA,tsRNA)是tRNA被切割而产生的。tsRNA具有重要的生物学功能,可发挥调节基因表达和调控蛋白质翻译等作用。近年来,研究揭示了tsRNA在癌症中的双重调控作用,特别是其在癌症患者体液中的显著差异性,强调了tsRNA作为一种潜在的肿瘤诊断和预后评估生物标志物的重要性。结直肠癌相关tsRNA中,5′tiRNA-His-GTG上调可促进肿瘤的发生和发展;由血管生成素切割产生的5′-tiRNA-Val上调,促进肿瘤转移和生长;tRF-20-MEJB5Y13上调,可促进结直肠癌细胞迁移和侵袭。胃癌相关tsRNA中,tRF-19-3L7L73JD上调可促进恶性肿瘤的进展,而tRF-24-V29K9UV3IU、tRF-5026a和tRF-Val上调可抑制肿瘤的增殖及进展。临床应用方面,血浆5-tRF-GlyGCC表达升高,诊断结直肠癌的曲线下面积达0.882,血浆tRF-5026a下降,诊断结直肠癌曲线下面积为0.883。胃癌患者血清tRF-27-FDXXE6XRK45、tRF-29-R9J8909NF5JP和tRF-23-Q99P9P9NDD的表达显著升高,诊断胃癌曲线下面积分别为0.805、0.889和0.783;三阴性乳腺癌血清中tDR-000620下降,与淋巴结转移和疾病复发相关。胃癌患者的血浆外泌体中,tRF-38、tRF-25和tRF-18表达升高,这些指标可用于诊断胃癌,且可能是术后预测因子;肝癌患者血浆外泌体的tRNA-ValTAC-3、tRNA-GlyTCC-5、tRNA-ValAAC-5和tRNA-GluCTC-5的表达水平明显增加,可能是新兴的标志物。本文综述了tsRNA的生成、分类及生物学功能,重点阐述tsRNA作为肿瘤标志物的研究进展以及其在不同肿瘤中发挥的作用。

Transfer RNA(tRNA)promotes the protein translation process by binding with corresponding amino acids and transporting them to the ribosome,emphasizing the vital role of tRNA in protein translation.Transfer RNA-derived small RNA(tsRNA)are fragments originating from tRNA and are produced when these tRNA are cleaved.As the degradation products of tRNA,tsRNA retain significant biological functions,notably in regulating gene expression and modulating translation.Recent researches have highlighted the dual regulatory role of tsRNA in oncology,especially their pronounced variations in the bodily fluids of cancer patients,accentuating the potential of tsRNA as biomarkers for cancer diagnosis and prognosis.Upregulation of tsRNA and 5′tiRNA His GTG related to colorectal cancer promotes tumor occurrence and development;Upregulation of 5′-tiRNA Val generated by angiopoietin cleavage promotes tumor metastasis and growth;Upregulation of tRF-20-MEJB5Y13 promotes the migration and invasion of colorectal cancer cells.Upregulation of gastric cancer related tsRNA,tRF-19-3L7L73JD,can promote the progression of malignant tumors,while upregulation of tRF-24-V29K9UV3IU,tRF-5026a,and tRF-Val may inhibit tumor proliferation and progression.In terms of clinical application,the expression of plasma 5-tRF-GlyGCC is increased,and the area under the curve for diagnosing colorectal cancer is 0.882.The plasma tRF-5026a is decreased,and the area under the curve for diagnosing colorectal cancer is 0.883.The expression of tRF-27-FDXXE6XRK45,tRF-29-R9J8909NF5JP,and tRF-23-Q99P9P9NDD in the serum of gastric cancer patients was significantly increased.The area under the diagnostic curve for gastric cancer was 0.805,0.889,and 0.783,respectively;The serum tDR-000620 in triple negative breast cancer decreased,which was related to lymph node metastasis and disease recurrence.In the plasma exosomes of gastric cancer patients,the expression of tRF-38,tRF-25,and tRF-18 is elevated,which can be used for diagnosis and may be a postoperative predictive factor.The expression levels of tRNA Val-TAC-3,tRNA GlyTCC-5,tRNA ValAAC-5,and tRNA GluCTC-5 in the plasma exosomes of liver cancer patients have significantly increased,which may be emerging biomarkers.This article reviews the biogenesis,classification,and biological functions of tsRNA,emphasizing the advancements in their application as tumor biomarkers and delineating their roles across various cancer types,offering insights into their utility in oncological research and clinical applications.