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Plasma tRNA Fragments Derived from 5' Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer.

ABSTRACT: Small RNAs derived from tRNAs are attracting considerable attention; however, the effects of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) as biomarkers have not been investigated in early-stage breast cancer (EBC). The study aimed to explore whether tRFs and tiRNAs could be detected in plasma and whether they could serve as diagnostic biomarkers. The study was conducted in four phases. Thirty tRFs and tiRNAs were selected by high-throughput sequencing in screening phase and then assessed in training, testing, and external validation phases by qRT-PCR. Six tRFs (tRF-Glu-CTC-003, tRF-Gly-CCC-007, tRF-Gly-CCC-008, tRF-Leu-CAA-003, tRF-Ser-TGA-001, and tRF-Ser-TGA-002) were found significantly downregulated in plasma samples of patients with EBC compared with normal controls, and all were derived from 5' ends of tRNAs. Patients with HER2+ EBC with low expression levels of tRF-Glu-CTC-003 were related to worse disease-free survival and overall survival. The identified tRFs were further examined in cell supernatants, exosomes isolated from plasma, and tissues. In conclusion, our study identified six tRFs from the 5' ends of tRNAs as novel diagnostic biomarkers for EBC, providing additional evidence for, and a better understanding of, circulating tRFs and EBC.

SUBMITTER: Wang J

PROVIDER: S-EPMC7452045 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Plasma tRNA Fragments Derived from 5' Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer.

Wang Jingyi J Ma Ge G Li Minghui M Han Xu X Xu Jin J Liang Mengdi M Mao Xinrui X Chen Xiang X Xia Tiansong T Liu Xiaoan X Wang Shui S

Molecular therapy. Nucleic acids 20200723

Small RNAs derived from tRNAs are attracting considerable attention; however, the effects of tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs) as biomarkers have not been investigated in early-stage breast cancer (EBC). The study aimed to explore whether tRFs and tiRNAs could be detected in plasma and whether they could serve as diagnostic biomarkers. The study was conducted in four phases. Thirty tRFs and tiRNAs were selected by high-throughput sequencing in screening phase and then assess ...[more]

PMID: 32814252

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Project description:BackgroundEarly diagnosis of nasopharyngeal carcinoma (NPC) is vital to improve the prognosis of these patients. However, early diagnosis of NPC is typically challenging. Therefore, we explored the pathogenetic roles and associated mechanisms of exosomes in plasma of patients with early-stage NPC.MethodsExosomes in plasma were extracted by ultra-high-speed centrifugation. Western blot and transmission electron microscopy (TEM) were used to verify the purity of exosomes. The sequencing data (6 plasma samples from healthy volunteers vs. 6 NPC plasma samples) were analyzed by principal component analysis (PCA), DESeq2, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and TargetScan. The differentially expressed miRNAs (DEmiRNAs) were obtained from the dataset (GSE118720) downloaded from the Gene Expression Omnibus (GEO) repository. Additionally, the datasets downloaded from the GEO database (GSE12452, GSE13597, GSE53819, GSE64634) were used to predict the target genes and functions of hsa-miR-1301-3p. qPCR was applied to verify the differences in the expressions of hsa-miR-1301-3p between 10 normal plasma and 10 NPC plasma samples.ResultsWestern blot, TEM, and Nanoparticle Tracking Analysis showed adequate purity of the extracted exosomes. RNA-seq analysis revealed 21 upregulated miRNAs, and 10 downregulated miRNAs in plasma exosomes of early-stage NPC patients. GO analysis showed that the target genes of DEmiRNAs were mainly enriched in DNA synthesis and transcription regulation. KEGG analysis revealed that DEmiRNAs were mainly enriched in PI3K-Akt and MAPK signaling pathways. Moreover, the expression of hsa-mir-1301-3p was verified to be significantly upregulated in enlarged samples of plasma exosomes.ConclusionsWe identified several DEmiRNAs extracted from tumor-derived exosomes between normal plasma and early-stage NPC plasma. Bioinformatics analyses indicated that these DEmiRNAs may be related to NPC development. Our study may provide novel insights into underlying biomarkers and mechanisms of plasma exosomes in early-stage NPC.

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Plasma tRNA Fragments Derived from 5' Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer.

Publications

Plasma tRNA Fragments Derived from 5' Ends as Novel Diagnostic Biomarkers for Early-Stage Breast Cancer.

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