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Int J Biol Sci 2019; 15(4):895-908. doi:10.7150/ijbs.29744

Research Paper

Systematic Analysis of tRNA-Derived Small RNAs Reveals Novel Potential Therapeutic Targets of Traditional Chinese Medicine (Buyang-Huanwu-Decoction) on Intracerebral Hemorrhage

Pengfei Li1, Tao Tang1, Tao Liu1,2, Jing Zhou1, Hanjin Cui1, Zehui He1, Yuanyuan Zhong1, En Hu1, Ali Yang3, Gaohui Wei4, Jiekun Luo1, Yang Wang1✉

1. Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, China
2. Department of Gerontology, Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University, Urumqi, China
3. Department of Neurology, Henan Province People's Hospital, Zhengzhou, China
4. Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

Abstract

Although Buyang-Huanwu-Decoction (BYHWD), a famous traditional Chinese medicine, has been utilized to promote the recovery of neurological function in intracerebral hemorrhage (ICH) for centuries, its therapeutic mechanisms remain unclear. tRNA-derived small RNA (tsRNA) is a novel class of short non-coding RNA, possessing potential regulating functions. In the current study, we explored the novel therapeutic targets of BYHWD by tsRNA-sequencing. Rats were randomly divided into three groups: sham, ICH, and BYHWD-treated groups. The modified neurological severity score, corner turn test, foot-fault test, and weight change were used to assess neurological injury. After BYHWD treatment, these behavioral tests were obviously meliorated compared with ICH group in the recovery phase. In the rat brain tissues surrounding the hemorrhagic region, a total of 350 tsRNAs for exact match were identified. 12 of tRNAs (fold change >1.3 and P-value <0.05) were significantly changed in ICH group compared to sham group. Among them, 3 of tRNAs (rno-tRFi-Ser-25a, rno-tRF5-Ala-16a and rno-tRF5-Glu-29a) were markedly regulated by BYHWD treatment and validated with quantitative real-time PCR. Additionally, target prediction and bioinformatics analyses revealed that these tsRNAs could play therapeutic roles through FoxO signaling pathway, positive regulation of long term synaptic depression, autophagy - animal, IL-17 signaling pathway and regulation of cytoskeleton and transforming growth factor beta. In conclusion, tsRNAs are the potential therapeutic targets of BYHWD on ICH treatment. The present study provides novel insights for future investigations to explore the mechanisms, by which BYHWD promotes neurological function recovery after ICH.

Keywords: traditional Chinese medicine, Buyang-Huanwu-Decoction, intracerebral hemorrhage, transcriptomics, non-coding RNA, tsRNA

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Li P, Tang T, Liu T, Zhou J, Cui H, He Z, Zhong Y, Hu E, Yang A, Wei G, Luo J, Wang Y. Systematic Analysis of tRNA-Derived Small RNAs Reveals Novel Potential Therapeutic Targets of Traditional Chinese Medicine (Buyang-Huanwu-Decoction) on Intracerebral Hemorrhage. Int J Biol Sci 2019; 15(4):895-908. doi:10.7150/ijbs.29744. Available from http://www.ijbs.com/v15p0895.htm