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

Huang, Peng; Tu, Biao; Liao, Huijun; Huang, Feizhou; Li, Zhenzhou; Zhu, Kuang-Ye; Dai, Feng; Liu, Huai-Zheng; Zhang, Tianyi; Sun, Chuanzheng

doi:10.1038/s41598-021-85421-0

Cited by 20 publications

(14 citation statements)

References 32 publications

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“…The presence of stable tsRNAs in human serum has been confirmed by recent studies (26). Expression profile of serum tsRNAs can be potential fingerprints for various diseases (29)(30)(31). To identify the tsRNA profile in SLE patients, all participants were divided into three groups according to the clinical standard, including SLE without LN, SLE with LN, and healthy control.…”

Section: Ectopic Serum Tsrna Profiles In Systemic Lupus Erythematosus Patientsmentioning

confidence: 94%

A Novel Serum tsRNA for Diagnosis and Prediction of Nephritis in SLE

et al. 2021

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ObjectiveDysregulation of transfer RNA (tRNA)-derived small noncoding RNA (tsRNA) signatures in human serum has been found in various diseases. Here, we determine whether the signatures of tsRNAs in serum can serve as biomarkers for diagnosis or prognosis of systemic lupus erythematosus (SLE).MethodsInitially, small RNA sequencing was employed for the screening serum tsRNAs obtained from SLE patients, followed by validation with TaqMan probe-based quantitative reverse transcription-PCR (RT-PCR) assay. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic efficacy. The biological functions of tsRNAs were identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) assay.ResultsWe first analyzed tsRNA signatures in SLE serum and identified that tRF-His-GTG-1 was significantly upregulated in SLE serum. The combination of tRF-His-GTG-1 and anti-dsDNA could serve as biomarkers for diagnosing SLE with a high area under the curve (AUC) of 0.95 (95% CI = 0.92–0.99), sensitivity (83.72%), and specificity (94.19%). Importantly, the noninvasive serum tRF-His-GTG-1 could also be used to distinguish SLE with LN or SLE without LN with AUC of 0.81 (95% CI, 0.73–0.88) and performance (sensitivity 66.27%, specificity 96.15%). Moreover, the serum tsRNA is mainly secreted via exosome and can directly target signaling molecules that play crucial roles in regulating the immune system.ConclusionIn this study, it has been demonstrated for the first time that serum tsRNAs can be employed as noninvasive biomarkers for the efficient diagnosis and prediction of nephritis in SLE.

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Section: Ectopic Serum Tsrna Profiles In Systemic Lupus Erythematosus Patientsmentioning

confidence: 94%

A Novel Serum tsRNA for Diagnosis and Prediction of Nephritis in SLE

et al. 2021

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“…[ 33 ] Recently, several studies have indicated that circulating tDRs could serve as potential biomarkers for cancer diagnosis, prognosis after oncological therapies, monitoring cancer progression, liver fibrosis diagnosis, and distinguishing between subtypes of acute stroke. [ 24 , 34 ] Because conventional methods for detecting tDRs may underestimate the diversity and abundance of extracellular tDRs, building the stress‐specific extracellular tDR signatures using specialized tDR sequencing techniques promises to provide new markers of cellular processes associated with disease pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Distinct Stress‐Dependent Signatures of Cellular and Extracellular tRNA‐Derived Small RNAs

Manning

Bagi

et al. 2022

Advanced Science

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The cellular response to stress is an important determinant of disease pathogenesis. Uncovering the molecular fingerprints of distinct stress responses may identify novel biomarkers and key signaling pathways for different diseases. Emerging evidence shows that transfer RNA‐derived small RNAs (tDRs) play pivotal roles in stress responses. However, RNA modifications present on tDRs are barriers to accurately quantifying tDRs using traditional small RNA sequencing. Here, AlkB‐facilitated methylation sequencing is used to generate a comprehensive landscape of cellular and extracellular tDR abundances in various cell types during different stress responses. Extracellular tDRs are found to have distinct fragmentation signatures from intracellular tDRs and these tDR signatures are better indicators of different stress responses than miRNAs. These distinct extracellular tDR fragmentation patterns and signatures are also observed in plasma from patients on cardiopulmonary bypass. It is additionally demonstrated that angiogenin and RNASE1 are themselves regulated by stressors and contribute to the stress‐modulated abundance of sub‐populations of cellular and extracellular tDRs. Finally, a sub‐population of extracellular tDRs is identified for which AGO2 appears to be required for their expression. Together, these findings provide a detailed profile of stress‐responsive tDRs and provide insight about tDR biogenesis and stability in response to cellular stressors.

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“…tsRNA is a non-coding small RNA which involved in a variety of physiological and pathological processes. It has been identified as a new class of NAFLD biomarkers due to the significant increase of tsRNAs in plasma of NAFLD patients [ 45 ]. Interestingly, we have previously reported that tsRNAs regulated autophagy, which played an important role in NASH [ 17 ].…”

Section: Discussionmentioning

confidence: 99%

The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway

et al. 2022

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Background Nonalcoholic steatohepatitis (NASH) is one of the most common liver diseases and has no safe and effective drug for treatment. We have previously reported the function of blueberry, but the effective monomer and related molecular mechanism remain unclear. Methods The monomer of blueberry was examined by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The NASH cell model was constructed by exposing HepG2 cells to free fatty acids. The NASH mouse model was induced by a high-fat diet for 12 weeks. NASH cell and mouse models were treated with different concentrations of blueberry monomers. The molecular mechanism was studied by Oil Red O staining, ELISA, enzyme activity, haematoxylin–eosin (H&E) staining, immunohistochemistry, immunofluorescence, western blot, RNA sequencing, and qRT-PCR. Results We identified one of the main monomer of blueberry as tectorigenin (TEC). Cyanidin-3-O glucoside (C3G) and TEC could significantly inhibit the formation of lipid droplets in steatosis hepatocytes, and the effect of TEC on the formation of lipid droplets was significantly higher than that of C3G. TEC can promote cell proliferation and inhibit the release of inflammatory mediators in NASH cell model. Additionally, TEC administration provided a protective role against high-fat diets induced lipid damage, and suppressed lipid accumulation. In NASH mouse model, TEC can activate autophagy, inhibit pyroptosis and the release of inflammatory mediators. In NASH cell model, TEC inhibited pyroptosis by stimulating autophagy. Then, small RNA sequencing revealed that TEC up-regulated the expression of tRF-47-58ZZJQJYSWRYVMMV5BO (tRF-47). The knockdown of tRF-47 blunted the beneficial effects of TEC on NASH in vitro, including inhibition of autophagy, activation of pyroptosis and release of inflammatory factors. Similarly, suppression of tRF-47 promoted the lipid injury and lipid deposition in vivo. Conclusions These results demonstrated that tRF-47-mediated autophagy and pyroptosis plays a vital role in the function of TEC to treat NASH, suggesting that TEC may be a promising drug for the treatment of NASH.

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

Cited by 20 publications

References 32 publications

A Novel Serum tsRNA for Diagnosis and Prediction of Nephritis in SLE

A Novel Serum tsRNA for Diagnosis and Prediction of Nephritis in SLE

Distinct Stress‐Dependent Signatures of Cellular and Extracellular tRNA‐Derived Small RNAs

The monomer TEC of blueberry improves NASH by augmenting tRF-47-mediated autophagy/pyroptosis signaling pathway

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