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

Deng Wei; Ben Niu; Bei Zhai; Xiao-Bai Liu; Yi-Long Yao; Chan-Chan Liang; Ping Wang

doi:10.1186/s12885-023-11532-8

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

BMC Cancer. 2023 Oct 20;23(1):1015. doi: 10.1186/s12885-023-11532-8.

Authors

Deng Wei^#^{1

2}, Ben Niu^#^{1

2}, Bei Zhai^{1

2}, Xiao-Bai Liu^{2

3}, Yi-Long Yao^{2

3}, Chan-Chan Liang^{1

2}, Ping Wang^{4

5}

Affiliations

¹ Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China.
² Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, China.
³ Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
⁴ Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China. wangping@cmu.edu.cn.
⁵ Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, China. wangping@cmu.edu.cn.

^# Contributed equally.

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.

Keywords: Glioma; Non-coding RNA; S100A11; tRF; tRNA-derived fragment.

MeSH terms

3' Untranslated Regions
Cell Differentiation
Cell Line
Glioma* / genetics
Humans
RNA, Transfer* / genetics
RNA, Transfer* / metabolism

Substances

3' Untranslated Regions
RNA, Transfer

Abstract

MeSH terms

Substances

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