Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis

Lei Zhu,Shuangyan Tan,Dan Sun,Yuanli Zuo,Qingbin Wu,Xiaomin Xu,Yu-Quan Wei,Youling Gong,Yun Zhao,Jiao Li,Xia-Wei Wei,Yong Peng

doi:10.1186/s12943-019-1000-8

Lei Zhu, Shuangyan Tan + Show 10 more

Open Access

https://doi.org/10.1186/s12943-019-1000-8

Copy DOI

Abstract

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.

Highlights

TRNA-derived small RNAs, usually 18~40 nucleotides in length, are novel small non-coding RNAs generated from precursor or mature tRNAs [1]. tsRNAs can be grouped into three distinctive classes, including precursor tRNA-derived small RNAs with the characteristic of poly U residues at 3′ terminus (3′ U tRFs), and mature tRNA-derived fragments as well as halves
Our results showed that 5% of exosomal small RNAs were generated from tRNAs, suggesting that tsRNAs could be incorporated into exosomes and secreted into extracellular environment (Fig. 1d)
Because tsRNAs generated from precursor tRNA have low levels in exosomes, so we focus on mature tRNA-derived tsRNAs that were further classified into tRNA-5 (5-termial of mature tRNA, 5′ tRF and 5′ tRH), tRF-i and tRNA-3 (3-termial of mature tRNA, 3′ tRF and 3′ tRH) according to their position (Additional file 1: Figure S2)

Summary

Open Access

Lei Zhu1†, Jiao Li1†, Youling Gong, Qingbin Wu1,3, Shuangyan Tan, Dan Sun, Xiaomin Xu1, Yuanli Zuo, Yun Zhao, Yu-Quan Wei, Xia-Wei Wei1* and Yong Peng1*. Abstract tRNA-derived small RNA (tsRNA) is a novel regulatory small non-coding RNA and participates in diverse physiological and pathological processes. 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. Our results expand non-coding RNA species in exosome, and highlight the potential of tsRNAs as a promising biomarker for cancer diagnosis. Main text tRNA-derived small RNAs (tsRNAs), usually 18~40 nucleotides (nt) in length, are novel small non-coding RNAs (sncRNAs) generated from precursor or mature tRNAs [1]. We demonstrate the presence and expression pattern of tsRNAs in exosomes from cell culture media and patients’ plasma, highlighting their potential for cancer diagnosis

Results and discussion

Conclusion

Additional files