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血浆来源的外泌体i-tRF-LeuCAA作为胶质瘤诊断的生物标志物及通过TPM4调控促进上皮-间质转化的因子

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

作者信息

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

机构信息

Medical School of Chinese PLA, Beijing, China.

Department of Neurosurgery, Hainan Hospital of Chinese PLA General Hospital, Sanya, Hainan, China.

出版信息

CNS Neurosci Ther. 2025 Apr;31(4):e70356. doi: 10.1111/cns.70356.

DOI:10.1111/cns.70356
PMID:40202170
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11979793/
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.

摘要

目的

本研究旨在发现可作为胶质瘤新型诊断生物标志物的血浆来源外泌体tsRNAs,并探究tsRNAs调控胶质瘤发展的机制。

方法

使用小RNA阵列测序鉴定胶质瘤患者血浆外泌体中差异表达的tsRNAs。利用生物信息学分析预测tsRNAs的生物学功能。检测用tsRNA模拟物和抑制剂处理的胶质瘤细胞表型变化。进一步分析潜在靶基因在胶质瘤中的诊断和预后特征及其相关功能。通过细胞和动物实验分析分子机制。

结果

使用小RNA测序在胶质瘤患者血浆来源外泌体中鉴定出的453个差异表达的tsRNAs中,i-tRF-LeuCAA与胶质瘤患者的预后和分子诊断特征相关,并促进胶质瘤细胞的迁移、侵袭和增殖,抑制其凋亡。此外,TPM4是i-tRF-LeuCAA的潜在靶标,且与胶质瘤中的上皮-间质转化有关。

结论

i-tRF-LeuCAA可作为胶质瘤诊断和预后的非侵入性生物标志物。i-tRF-LeuCAA可能间接调节TPM4表达并影响上皮-间质转化,从而促进胶质瘤进展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/41c8a5694bc7/CNS-31-e70356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/8f71d06e29f4/CNS-31-e70356-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/078b1ad22348/CNS-31-e70356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/0e06faf725c2/CNS-31-e70356-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/a0235848b3ce/CNS-31-e70356-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/efb76e47bad4/CNS-31-e70356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/9803a4e11e74/CNS-31-e70356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/ac508730e970/CNS-31-e70356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/1e00743d54fd/CNS-31-e70356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/570cafeed0b3/CNS-31-e70356-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/41c8a5694bc7/CNS-31-e70356-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/8f71d06e29f4/CNS-31-e70356-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/078b1ad22348/CNS-31-e70356-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/0e06faf725c2/CNS-31-e70356-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/a0235848b3ce/CNS-31-e70356-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/efb76e47bad4/CNS-31-e70356-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/9803a4e11e74/CNS-31-e70356-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/ac508730e970/CNS-31-e70356-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/1e00743d54fd/CNS-31-e70356-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/570cafeed0b3/CNS-31-e70356-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66ba/11979793/41c8a5694bc7/CNS-31-e70356-g002.jpg

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Hypoxic glioma cell-secreted exosomal circ101491 promotes the progression of glioma by regulating miR-125b-5p/EDN1.缺氧胶质瘤细胞分泌的外泌体circ101491通过调控miR-125b-5p/EDN1促进胶质瘤进展。
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An old friend with a new face: tRNA-derived small RNAs with big regulatory potential in cancer biology.旧友新颜:tRNA 衍生的小 RNA 在癌症生物学中具有巨大的调控潜力。
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