Table2_Expression Profiles of tRNA-Derived Small RNAs and Their Potential Roles in Primary Nasopharyngeal Carcinoma.XLSX

Introduction: tRNA-derived small RNAs (tsRNAs), a class of small non-coding RNAs, are divided into two categories: tRNA-related fragments (tRFs) and tRNA halves (tiRNAs). Abnormal expression of tsRNAs has been found in diverse cancers, which indicates that further understanding of the function of tsRNAs will help identify new biomarkers and potential therapeutic targets. Until now, the underlying roles of tsRNAs in primary nasopharyngeal carcinoma (NPC) are still unknown.
Methods: tRF and tiRNA sequencing was performed on four pairs of NPC tissues and healthy controls. Thirty pairs of NPC samples were used for quantitative real-time polymerase chain reaction (qRT-PCR) verification, and the ROC analysis was used to evaluate the diagnostic efficiency initially. Target prediction and bioinformatics analysis of validated tRFs and tiRNAs were conducted to explore the mechanisms of tsRNAs in NPC’s pathogenesis.
Results: A total of 158 differentially expressed tRFs and tiRNAs were identified, of which 88 are upregulated and 70 are downregulated in NPC. Three validated tRFs in the results of qRT-PCR were consistent with the sequencing data: two upregulations (tRF-1:28-Val-CAC-2 and tRF-1:24-Ser-CGA-1-M3) and one downregulation (tRF-55:76-Arg-ACG-1-M2). The GO and KEGG pathway enrichment analysis showed that the potential target genes of validated tRFs are widely enriched in cancer pathways. The related modules may play an essential role in the pathogenesis of NPC.
Conclusions: The tsRNAs may become a novel class of biological diagnostic indicators and possible targets for NPC.

引言：转运RNA衍生小RNA（tRNA-derived small RNAs，tsRNAs）是一类非编码小RNA，可分为tRNA相关片段（tRNA-related fragments，tRFs）和tRNA半分子（tRNA halves，tiRNAs）两类。现有研究已在多种癌症中发现tsRNAs的表达异常，这提示深入解析tsRNAs的功能将有助于发现新型生物标志物与潜在治疗靶点。截至目前，tsRNAs在原发性鼻咽癌（nasopharyngeal carcinoma，NPC）中的潜在作用机制仍未明确。
方法：本研究对4对鼻咽癌组织与健康对照组织开展了tRF和tiRNA测序；选取30对鼻咽癌样本用于定量实时聚合酶链反应（quantitative real-time polymerase chain reaction，qRT-PCR）验证，并通过ROC分析初步评估其诊断效能。此外，对验证后的tRFs与tiRNAs进行靶基因预测及生物信息学分析，以探索tsRNAs在鼻咽癌发病机制中的作用。
结果：本研究共鉴定出158个差异表达的tRFs与tiRNAs，其中在鼻咽癌组织中88个表达上调，70个表达下调。qRT-PCR验证结果显示，3个tRFs的表达变化与测序数据一致：2个表达上调（tRF-1:28-Val-CAC-2和tRF-1:24-Ser-CGA-1-M3），1个表达下调（tRF-55:76-Arg-ACG-1-M2）。基因本体（Gene Ontology，GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）通路富集分析结果表明，验证后tRFs的潜在靶基因广泛富集于癌症相关通路，相关调控模块可能在鼻咽癌的发病过程中发挥关键作用。
结论：tsRNAs有望成为鼻咽癌新型生物诊断指标及潜在治疗靶点。