Elevation of plasma tRNA fragments as a promising biomarker for liver fibrosis in nonalcoholic fatty liver disease

• Published in: Scientific reports Vol. 11; no. 1; p. 5886
• Main Authors: Huang, Peng, Tu, Biao, Liao, Hui-jun, Huang, Fei-zhou, Li, Zhen-zhou, Zhu, Kuang-ye, Dai, Feng, Liu, Huai-zheng, Zhang, Tian-yi, Sun, Chuan-zheng
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.03.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/4020/4021/1607/1605; 692/4020/4021/1607/2750; 692/4020/4021/1607/2751; Adult; Aged; Animal models; Animals; Base Sequence; Biomarkers; Biomarkers - blood; Blood; Disease Models, Animal; Disease Progression; Fatty liver; Female; Fibrosis; Gene Expression Profiling; Humanities and Social Sciences; Humans; Liver; Liver - metabolism; Liver Cirrhosis - blood; Liver diseases; Male; Mice; Mice, Inbred BALB C; Middle Aged; multidisciplinary; Non-alcoholic Fatty Liver Disease - blood; Plasma; Plasma levels; RNA, Transfer - blood; RNA, Transfer - chemistry; RNA, Transfer - genetics; Science; Science (multidisciplinary); tRNA; Up-Regulation - genetics; Young Adult
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-85421-0

Fibrotic tissue remodelling in nonalcoholic fatty liver disease (NAFLD) will probably emerge as the leading cause of end-stage liver disease in the coming decades, but the ability to diagnose liver fibrosis in NAFLD patients noninvasively is limited. The abnormal expression of tRNA-derived small RNA (tsRNA) in plasma provides a novel idea for noninvasive diagnosis of various diseases, however, the relationship between tsRNAs and NAFLD is still unknown. Here, we took advantage of small RNA-Seq technology to profile tsRNAs in NAFLD patients and found the ubiquitous presence of hepatic tsRNAs secreted into circulating blood. Verification in a cohort of 114 patients with NAFLD and 42 patients without NAFLD revealed that three tsRNAs (tRF-Val-CAC-005, tiRNA-His-GTG-001, and tRF-Ala-CGC-006) were significantly elevated in the plasma of NAFLD patients, and the expression level are associated with NAFLD activity score (calculated from 0 to 8) and fibrosis stage (scored from 0 to 4). In mouse models, we further found that increased plasma levels of these three tsRNAs were positively correlated with the degree of liver fibrosis. Our study potentially identifies a new class of NAFLD biomarkers and reveal the possible existence of tsRNAs in the blood that can be used to predict fibrogenesis risk in patients diagnosed with NAFLD.