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Exosomal tRNA-derived Small RNA as a Promising Biomarker for Cancer Diagnosis


Exosomal tRNA-derived Small RNA as a Promising Biomarker for Cancer Diagnosis

Lei Zhu et al. Mol Cancer.


tRNA-derived small RNA (tsRNA) is a novel regulatory small non-coding RNA and participates in diverse physiological and pathological processes. However, the presence of tsRNAs in exosome and their diagnostic potential remain unclear. In this study, we took advantage of small RNA-seq technology to profile exosomal tsRNAs from cell culture medium and plasma, and found ubiquitous presence of tsRNAs in exosome. To explore the potential value of tsRNA for cancer diagnosis, we compared exosomal tsRNA levels between liver cancer patients and healthy donors, revealing that tsRNAs were dramatically increased in plasma exosomes of liver cancer patients. Importantly, patients with liver cancer exhibited significantly higher levels of four tsRNAs (tRNA-ValTAC-3, tRNA-GlyTCC-5, tRNA-ValAAC-5 and tRNA-GluCTC-5) in plasma exosome, demonstrating that plasma exosomal tsRNA could serve as a novel diagnostic biomarker. Taken together, our results not only expand non-coding RNA species in exosome, but also highlight the potential of tsRNAs as a promising biomarker for cancer diagnosis.

Keywords: Biomarker; Exosome; Non-coding RNA; Plasma; tRNA-derived small RNA.

Conflict of interest statement

Ethics approval and consent to participate

Sample collections were approved by Ethnics Committee of West China Hospital, Sichuan University. The informed consents were obtained from patients or their guardians, as appropriate.

Consent for publication

All authors give consent for the publication of the manuscript in Molecular Cancer.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


Fig. 1
Fig. 1
Profiling of tsRNAs in exosomes from cell culture medium. a Exosome collection procedure from SK-Hep1 cell culture medium; b Transmission electron micrograph (TEM) of exosomes isolated from cell culture medium (The scale bar is 100 nm); c Correlation analysis of two small RNA-seq replicates; d Percentage of each type of small RNAs in exosomes; e Percentage of each type of tsRNAs in exosomes; f Percentage of tRNA-5 generated from Glu-, Gly-, Lys- and Val-tRNA; g Length distribution of total tRNA-5s; h Length distribution of the tRNA-5s derived from Glu-, Gly-, Lys- and Val-tRNA; i Relative quantification of tsRNAs in SK-Hep1 cells and exosomes from cell culture medium
Fig. 2
Fig. 2
Profiling of tsRNAs in exosomes from plasma. a, b Relative expression of tsRNAs (a) and tRNA-5 (b) in exosomes from liver cancer patients and healthy donors; c Length distribution of tRNA-5 in exosomes from plasma; d Heatmap of differentially expressed tsRNAs between liver cancer patients and healthy donors. N1-N5: five healthy controls; T1-T5: five liver cancer patients
Fig. 3
Fig. 3
Validation of plasma exosomal tsRNAs in liver cancer patients and healthy controls. a-d RT-qPCR analyses of exosomal tRNA-ValTAC-3 (a), tRNA-GlyTCC-5 (b), tRNA-ValAAC-5 (c) and tRNA-GluCTC-5 (d) between healthy controls and liver cancer patients. miR-16 was used for normalization. P value of Student’s t-test: *p ≤ 0.05, **p ≤ 0.01

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