Expression profiles and function prediction of tRNA-derived fragments in glioma

Abstract Background Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown. Methods The...

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Main Authors: Deng Wei, Ben Niu, Bei Zhai, Xiao-bai Liu, Yi-long Yao, Chan-chan Liang, Ping Wang
Format: Article
Language:English
Published: BMC 2023-10-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-023-11532-8
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author Deng Wei
Ben Niu
Bei Zhai
Xiao-bai Liu
Yi-long Yao
Chan-chan Liang
Ping Wang
author_facet Deng Wei
Ben Niu
Bei Zhai
Xiao-bai Liu
Yi-long Yao
Chan-chan Liang
Ping Wang
author_sort Deng Wei
collection DOAJ
description Abstract Background Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown. Methods The expression profiles of tRF subtypes were analyzed using the Cancer Genome Atlas (TCGA)-low-grade gliomas (LGG)/GBM dataset. The target genes of tRFs were subjected to Gene Ontology, Kyoto Encyclopedia and Gene set enrichment analysis of Genes and Genomes pathway enrichment analysis. The protein-protein interaction enrichment analysis was performed by STRING. QRT-PCR was performed to detect the expressions of tRFs in human glioma cell lines U87, U373, U251, and human astrocyte cell line SVG p12. Western blot assay was used to detect to the expression of S100A11. The interaction between tRF-19-R118LOJX and S100A11 mRNA 3’UTR was detected by dual-luciferase reporter assay. The effects of tRF-19-R118LOJX, tRF-19-6SM83OJX and S100A11 on the glioma cell proliferation, migration and in vitro vasculogenic mimicry formation ability were examined by CCK-8 proliferation assay, EdU assay, HoloMonitor cell migration assay and tube formation assay, respectively. Results tRF-19-R118LOJX and tRF-19-6SM83OJX are the most differentially expressed tRFs between LGG and GBM groups. The functional enrichment analysis showed that the target genes of tRF-19-R118LOJX and tRF-19-6SM83OJX are enriched in regulating blood vessel development. The upregulated target genes are linked to adverse survival outcomes in glioma patients. tRF-19-R118LOJX and tRF-19-6SM83OJX were identified to suppress glioma cell proliferation, migration, and in vitro vasculogenic mimicry formation. The mechanism of tRF-19-R118LOJX might be related to its function as an RNA silencer by targeting the S100A11 mRNA 3’UTR. Conclusion tRFs would become novel diagnostic biomarkers and therapeutic targets of glioma, and the mechanism might be related to its post-transcriptionally regulation of gene expression by targeting mRNA 3’UTR.
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spelling doaj.art-dd26a97824e04e018dfc84503ea38b812023-11-20T09:43:20ZengBMCBMC Cancer1471-24072023-10-0123111810.1186/s12885-023-11532-8Expression profiles and function prediction of tRNA-derived fragments in gliomaDeng Wei0Ben Niu1Bei Zhai2Xiao-bai Liu3Yi-long Yao4Chan-chan Liang5Ping Wang6Department of Neurobiology, School of Life Sciences, China Medical UniversityDepartment of Neurobiology, School of Life Sciences, China Medical UniversityDepartment of Neurobiology, School of Life Sciences, China Medical UniversityKey Laboratory of Neuro-oncology in Liaoning ProvinceKey Laboratory of Neuro-oncology in Liaoning ProvinceDepartment of Neurobiology, School of Life Sciences, China Medical UniversityDepartment of Neurobiology, School of Life Sciences, China Medical UniversityAbstract Background Glioblastoma (GBM) is the most aggressive malignant primary brain tumor. The transfer RNA-derived fragments (tRFs) are a new group of small noncoding RNAs, which are dysregulated in many cancers. Until now, the expression and function of tRFs in glioma remain unknown. Methods The expression profiles of tRF subtypes were analyzed using the Cancer Genome Atlas (TCGA)-low-grade gliomas (LGG)/GBM dataset. The target genes of tRFs were subjected to Gene Ontology, Kyoto Encyclopedia and Gene set enrichment analysis of Genes and Genomes pathway enrichment analysis. The protein-protein interaction enrichment analysis was performed by STRING. QRT-PCR was performed to detect the expressions of tRFs in human glioma cell lines U87, U373, U251, and human astrocyte cell line SVG p12. Western blot assay was used to detect to the expression of S100A11. The interaction between tRF-19-R118LOJX and S100A11 mRNA 3’UTR was detected by dual-luciferase reporter assay. The effects of tRF-19-R118LOJX, tRF-19-6SM83OJX and S100A11 on the glioma cell proliferation, migration and in vitro vasculogenic mimicry formation ability were examined by CCK-8 proliferation assay, EdU assay, HoloMonitor cell migration assay and tube formation assay, respectively. Results tRF-19-R118LOJX and tRF-19-6SM83OJX are the most differentially expressed tRFs between LGG and GBM groups. The functional enrichment analysis showed that the target genes of tRF-19-R118LOJX and tRF-19-6SM83OJX are enriched in regulating blood vessel development. The upregulated target genes are linked to adverse survival outcomes in glioma patients. tRF-19-R118LOJX and tRF-19-6SM83OJX were identified to suppress glioma cell proliferation, migration, and in vitro vasculogenic mimicry formation. The mechanism of tRF-19-R118LOJX might be related to its function as an RNA silencer by targeting the S100A11 mRNA 3’UTR. Conclusion tRFs would become novel diagnostic biomarkers and therapeutic targets of glioma, and the mechanism might be related to its post-transcriptionally regulation of gene expression by targeting mRNA 3’UTR.https://doi.org/10.1186/s12885-023-11532-8GliomatRNA-derived fragmenttRFNon-coding RNAS100A11
spellingShingle Deng Wei
Ben Niu
Bei Zhai
Xiao-bai Liu
Yi-long Yao
Chan-chan Liang
Ping Wang
Expression profiles and function prediction of tRNA-derived fragments in glioma
BMC Cancer
Glioma
tRNA-derived fragment
tRF
Non-coding RNA
S100A11
title Expression profiles and function prediction of tRNA-derived fragments in glioma
title_full Expression profiles and function prediction of tRNA-derived fragments in glioma
title_fullStr Expression profiles and function prediction of tRNA-derived fragments in glioma
title_full_unstemmed Expression profiles and function prediction of tRNA-derived fragments in glioma
title_short Expression profiles and function prediction of tRNA-derived fragments in glioma
title_sort expression profiles and function prediction of trna derived fragments in glioma
topic Glioma
tRNA-derived fragment
tRF
Non-coding RNA
S100A11
url https://doi.org/10.1186/s12885-023-11532-8
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