Plasma-Derived Exosomal i-tRF-LeuCAA as Biomarker for Glioma Diagnosis and Promoter of Epithelial-Mesenchymal Transition via TPM4 Regulation

IF 4.8 1区医学 Q1 NEUROSCIENCES

CNS Neuroscience & Therapeutics Pub Date : 2025-04-09 DOI:10.1111/cns.70356

Hongyu Liu, Wentao Hu, Lijun Zhang, Ze Li, Jialin Liu, Ling Chen

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Abstract

Aims

This study aimed to discover plasma-derived exosomal tsRNAs that serve as novel diagnostic biomarkers for glioma and to investigate the mechanism by which tsRNAs regulate glioma development.

Methods

Differentially expressed tsRNAs in the plasma exosomes of glioma patients were identified using small RNA array sequencing. Bioinformatics analyses were used to predict the biological function of tsRNAs. The changes in the phenotypes of glioma cells treated with a tsRNA mimic and inhibitor were detected. The diagnostic and prognostic characteristics of potential target genes and their related functions in gliomas were further analyzed. The cell and animal experiments were used to analyze the molecular mechanisms.

Results

Among the 453 differentially expressed tsRNAs identified in the plasma-derived exosomes of glioma patients using small RNA sequencing, i-tRF-LeuCAA was associated with the prognosis and molecular diagnostic characteristics of glioma patients and promoted the migration, invasion, and proliferation of glioma cells and inhibited their apoptosis. In addition, TPM4 is a potential target of i-tRF-LeuCAA and is related to epithelial–mesenchymal transition in gliomas.

Conclusions

i-tRF-LeuCAA could be served as a non-invasive biomarker in the diagnosis and prognosis of glioma. i-tRF-LeuCAA may indirectly regulate TPM4 expression and influence epithelial–mesenchymal transition, which may promote glioma progression.

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血浆源性外泌体i-tRF-LeuCAA作为胶质瘤诊断的生物标志物，并通过TPM4调控促进上皮-间质转化

本研究旨在发现可作为胶质瘤诊断标志物的血浆源性外泌体tsRNAs，并探讨tsRNAs调控胶质瘤发展的机制。方法采用小RNA阵列测序技术对胶质瘤患者血浆外泌体中差异表达的tsRNAs进行鉴定。生物信息学分析用于预测tsRNAs的生物学功能。检测了用tsRNA模拟物和抑制剂处理的胶质瘤细胞表型的变化。进一步分析脑胶质瘤中潜在靶基因的诊断和预后特点及其相关功能。通过细胞实验和动物实验对其分子机制进行了分析。结果利用小RNA测序技术在胶质瘤患者血浆源性外泌体中鉴定出453种差异表达的tsRNAs，其中i-tRF-LeuCAA与胶质瘤患者的预后和分子诊断特征相关，促进胶质瘤细胞的迁移、侵袭和增殖，抑制胶质瘤细胞的凋亡。此外，TPM4是i-tRF-LeuCAA的潜在靶点，与胶质瘤的上皮-间质转化有关。结论i-tRF-LeuCAA可作为胶质瘤诊断和预后的无创生物标志物。i-tRF-LeuCAA可能间接调节TPM4表达并影响上皮-间质转化，从而促进胶质瘤的进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

CNS Neuroscience & Therapeutics 医学-神经科学

CiteScore

7.30

自引率

12.70%

发文量

240

审稿时长

2 months

期刊介绍： CNS Neuroscience & Therapeutics provides a medium for rapid publication of original clinical, experimental, and translational research papers, timely reviews and reports of novel findings of therapeutic relevance to the central nervous system, as well as papers related to clinical pharmacology, drug development and novel methodologies for drug evaluation. The journal focuses on neurological and psychiatric diseases such as stroke, Parkinson’s disease, Alzheimer’s disease, depression, schizophrenia, epilepsy, and drug abuse.