{"title":"Exploring the Role of tRNA-Derived Fragments in Pterygium: Molecular Insights into tsRNA-Mediated Fibroblast Regulation and Disease Progression.","authors":"Qiaodan Yang, Xinyu Tang, Ruiying Zhang, Yulian Dou, Ming Yan, Fang Zheng","doi":"10.2174/0109298673361701250321082610","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pterygium is a common ocular surface disorder characterized by fibrovascular overgrowth, with recurrence remaining a major clinical challenge. While non-coding RNAs have been implicated in pterygium pathogenesis, the role of tRNA- derived small RNAs (tsRNAs) remains unexplored.</p><p><strong>Methods: </strong>We performed small RNA sequencing on pterygium and adjacent normal conjunctiva tissues to profile tsRNA expression. Differentially expressed tsRNAs were validated using qRT-PCR, and their biological functions were investigated via cell proliferation and wound healing assays in human pterygium fibroblasts (HPF). Potential target genes and enriched pathways were analyzed using bioinformatics approaches, including KEGG and GO enrichment analysis.</p><p><strong>Results: </strong>We identified significantly dysregulated tsRNAs in pterygium, with tRF- 1_30-His- GTG-1, tRF-1_31-Val-CAC-2, tRF-1_31-Gly-GCC-1, and tRF-1_30-Gly- CCC-1-M4 exhibiting notable upregulation. Functional assays demonstrated that tRF- 1_30-His- GTG-1 promotes fibroblast proliferation and migration, while the other three tsRNAs enhance fibroblast migration. Pathway enrichment analysis revealed their involvement in cellular proliferation, extracellular matrix remodeling, and angiogenesis.</p><p><strong>Conclusion: </strong>This study provides the first evidence of tsRNA involvement in pterygium pathogenesis, highlighting their potential as biomarkers and therapeutic targets. Future studies should focus on deciphering their precise regulatory mechanisms and developing RNA-based therapeutic strategies to mitigate disease progression.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0109298673361701250321082610","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Pterygium is a common ocular surface disorder characterized by fibrovascular overgrowth, with recurrence remaining a major clinical challenge. While non-coding RNAs have been implicated in pterygium pathogenesis, the role of tRNA- derived small RNAs (tsRNAs) remains unexplored.
Methods: We performed small RNA sequencing on pterygium and adjacent normal conjunctiva tissues to profile tsRNA expression. Differentially expressed tsRNAs were validated using qRT-PCR, and their biological functions were investigated via cell proliferation and wound healing assays in human pterygium fibroblasts (HPF). Potential target genes and enriched pathways were analyzed using bioinformatics approaches, including KEGG and GO enrichment analysis.
Results: We identified significantly dysregulated tsRNAs in pterygium, with tRF- 1_30-His- GTG-1, tRF-1_31-Val-CAC-2, tRF-1_31-Gly-GCC-1, and tRF-1_30-Gly- CCC-1-M4 exhibiting notable upregulation. Functional assays demonstrated that tRF- 1_30-His- GTG-1 promotes fibroblast proliferation and migration, while the other three tsRNAs enhance fibroblast migration. Pathway enrichment analysis revealed their involvement in cellular proliferation, extracellular matrix remodeling, and angiogenesis.
Conclusion: This study provides the first evidence of tsRNA involvement in pterygium pathogenesis, highlighting their potential as biomarkers and therapeutic targets. Future studies should focus on deciphering their precise regulatory mechanisms and developing RNA-based therapeutic strategies to mitigate disease progression.
背景：翼状胬肉是一种常见的眼表疾病，以纤维血管过度生长为特征，其复发仍然是一个主要的临床挑战。虽然非编码rna与翼状胬肉的发病机制有关，但tRNA衍生的小rna （tsRNAs）的作用仍未被探索。方法：对翼状胬肉和相邻正常结膜组织进行小RNA测序，分析tsRNA的表达。采用qRT-PCR验证了差异表达的tsRNAs，并通过人翼状胬肉成纤维细胞（HPF）的细胞增殖和伤口愈合实验研究了其生物学功能。利用生物信息学方法分析潜在靶基因和富集途径，包括KEGG和GO富集分析。结果：我们在翼状胬肉中发现了显著失调的tsRNAs，其中tRF- 1_30-His- GTG-1、tRF-1_31- val - ca -2、tRF-1_31- gly - cc -1和tRF-1_30- gly - cc -1- m4表现出显著的上调。功能分析表明，tRF- 1_30-His- GTG-1促进成纤维细胞增殖和迁移，而其他三种tsRNAs则促进成纤维细胞迁移。途径富集分析显示它们参与细胞增殖、细胞外基质重塑和血管生成。结论：本研究首次提供了tsRNA参与翼状胬肉发病机制的证据，突出了其作为生物标志物和治疗靶点的潜力。未来的研究应侧重于破译它们的精确调控机制，并开发基于rna的治疗策略来减缓疾病进展。
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Aims & Scope
Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. The journal also publishes reviews on recent patents. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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