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Clinical utility and biological function of Transfer RNA-derived small RNAs in Patients with Acute Coronary Syndrome [ncRNA-seq]

ABSTRACT: Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. Aberrant expression of Transfer RNA-derived small RNAs (tsRNA) contributed to various human disease. However, the clincal utility and biological function of tsRNA in ACS are largely unknown. High throughput sequencing revealed a landscape of novel sncRNAs in the human PBMCs. tsRNAs represented a characteristic expression pattern in responding to acute coronary syndrome; tRF-Gly-GCC-06 and tRF-Lys-CTT-02 were significantly up-regulated in patients with unstable angina(UA) and acute myocardial infarction(AMI). Both of the two tRFs demonstrated reasonable diagnostic accuracy for ACS detection. tRF-Gly-GCC-06 and tRF-Lys-CTT-02 upregulation were independent predictors of an increased risk of ACS. Both of the two tRFs expression levels show a significantly positive correlation with Gensini score.Our study identified novel tsRNA alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets.

ORGANISM(S): Homo sapiens

PROVIDER: GSE279974 | GEO | 2025/04/30

REPOSITORIES: GEO

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Clinical utility and biological function of Transfer RNA-derived small RNAs in Patients with Acute Coronary Syndrome [RNA-seq]

Project description:Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. Aberrant expression of Transfer RNA-derived small RNAs (tsRNA) contributed to various human disease. However, the clincal utility and biological function of tsRNA in ACS are largely unknown. High throughput sequencing revealed a landscape of novel sncRNAs in the human PBMCs. tsRNAs represented a characteristic expression pattern in responding to acute coronary syndrome; tRF-Gly-GCC-06 and tRF-Lys-CTT-02 were significantly up-regulated in patients with unstable angina(UA) and acute myocardial infarction(AMI). Both of the two tRFs demonstrated reasonable diagnostic accuracy for ACS detection. tRF-Gly-GCC-06 and tRF-Lys-CTT-02 upregulation were independent predictors of an increased risk of ACS. Both of the two tRFs expression levels show a significantly positive correlation with Gensini score.Our study identified novel tsRNA alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets.

2025-04-30 | GSE279975 | GEO

tRF&tiRNA sequencing of human PTC tissues and corresponding paracancer tissues

Project description:Purpose: To study the expression and potential significance of tRF and tiRNA in PTC (Papillary thyroid carcinoma) by sequencing tRF and tiRNA in PTC tissues and corresponding paracancer tissues of thyroid cancer patients. Methods: Four pairs of PTC tissues and paracancer tissues were collected. Small RNA sequencing was performed on Illumina NexSeq instrument. Results: If P ≤ 0.05, fold change > 1.5 as the cutoff, there were 27 up-regulated tRFs & tiRNAs and 20 down-regulated tRFs & tiRNAs. Conclusions: Among the differentially expressed tRFs & tiRNAs, tiRNA-1:34-Lys-CTT-2 and tRF-1:30-Gly-CCC-3 may be the potential novel regulatory factors.

2022-02-26 | GSE197438 | GEO

Maternal Serum tRNA-derived Fragments (tRFs) as Potential Candidates for Diagnosis of Fetal Congenital Heart Disease

Project description:Background: Congenital heart disease (CHD) is one of the most predominant birth defects that cause infant death worldwide. The timely and successful surgical treatment of CHD on newborns after delivery requires accurate detection and reliable diagnosis during pregnancy. However, there are no biomarkers that can serve as an early diagnostic factor for CHD patients. tRNA-derived fragments (tRFs) have been reported to play an important role in the occurrence and progression of numerous diseases, but their roles in CHD remains unknown. Methods: High-throughput sequencing was performed on the peripheral blood of pregnant women with abnormal fetal heart and normal fetal heart, and 728 differentially expressed tRFs/tiRNAs were identified, among which the top 18 tRFs/tiRNAs were selected as predictive biomarkers of CHD. Then, quantitative reverse transcriptase polymerase chain reaction verified the expression of tRFs/tiRNAs in more clinical samples, and the correlation between tRFs/tiRNAs abnormalities and CHD was analyzed. Results: tRF-58:74-Gly-GCC-1 and tiRNA-1:35-Leu-CAG-1-M2 may be promising biomarkers. Through further bioinformatics analysis, we predicted that TRF-58:744-GLy-GCC-1 could induce CHD by influencing biological metabolic processes. Conclusions: our results provide a theoretical basis for the abnormally expressed tRF-58:74-Gly-GCC-1 in maternal peripheral blood as a new potential biomarker for the accurate diagnosis of CHD during pregnancy.

2023-03-01 | GSE221349 | GEO

tsRNAs Are Potential Biomarkers of Acute Rejection in Vascularized Composite Allotransplantation

Project description:Purpose: to explore the function and mechanism of acute rejection in vascularized composite allotransplantation Method: tRF & tiRNA profiles of acute rejection in vascularized composite allotransplantation were generated by deep sequencing, using Illumina NextSeq 500. qRT–PCR validation was performed using SYBR Green assays. Results:Sequencing was used to screen expression profiles and predict target genes. Compared with the control group, there were significant differences in the expression levels of 16 tRFs & tiRNAs, including 5 up-regulated target genes and 11 down-regulated target genes. Bioinformatics analysis and RT-qPCR revealed potential up regulation of tRFs & tiRNAs(tiRNA-1-33-Gly-GCC-1, tiRNA-1-34-Glu-CTC-1, tRF-1-32-Gly-GCC-2-M2) and down regulation of tRFs & tiRNAs (tRF-59:75-Gln-CTG-2-M2, tRF-59:76-Val-AAC-1-M2). Conclusion: In conclusion, it is speculated that tiRNA-1-34-Glu-CTC-1 plays an important role in VCA induced acute rejection by regulating CACNA1D gene in MAPK signaling pathway. This provides a new insight into the mechanism and therapeutic targets of acute rejection.

2022-07-20 | GSE190008 | GEO

Differential Expression Spectrum of tRNA-Derived small RNAs in Idiopathic Pulmonary Arterial Hypertension

Project description:Microarray detected 816 statistically differentially expressed tsRNAs, of which 243 tsRNAs were upregulated and 573 were downregulated. Eight validated tsRNAs in the results of Real Time-PCR were consistent with the small RNA microarray: four upregulations (tRF3a-AspGTC-9, 5'tiRNA-31-GluCTC-16, i-tRF-31:54-Val-CAC-1 and tRF3b-TyrGTA-4) and four downregulation (5'tiRNA-33-LysTTT-4, i-tRF-8:32-Val-AAC-2, i-tRF-2:30-His-GTG-1, and i-tRF-15:31-Lys-CTT-1).

2023-06-30 | GSE228750 | GEO

Control of noncoding RNA production and histone levels by a 5’ tRNA fragment

Project description:Small RNAs derived from mature tRNAs, referred to as tRNA fragments or “tRFs”, are an emerging class of regulatory RNAs with poorly understood functions in cellular regulation. We recently identified a role for one specific tRF – 5’ tRF-Gly-GCC, or tRF-GG – in repression of genes associated with the endogenous retroelement MERVL, but the mechanistic basis for this regulation was unknown. Here, we show that tRF-GG plays a role in production of a wide variety of noncoding RNAs normally synthesized in Cajal bodies. Among these noncoding RNAs, tRF-GG regulation of the U7 snRNA modulates heterochromatin-mediated transcriptional repression of MERVL elements by supporting an adequate supply of histone proteins. Importantly, the effects of inhibiting tRF-GG on histone mRNA levels, activity of a histone 3’ UTR reporter, and ultimately on MERVL regulation could all be suppressed by the U7 RNA. We show that the related RNA-binding proteins hnRNPF and H bind directly to tRF-GG, and are required for Cajal body biogenesis. Together, our data reveal a conserved mechanism for 5’ tRNA fragment control of noncoding RNA biogenesis and, consequently, in global chromatin organization.

2020-01-17 | GSE127247 | GEO

Effect of tRF-1-Ser on the gene expression of breast cancer cell MDA-MB-453

Project description:tRNA-derived small RNAs (tsRNA) are a new type of noncoding RNAs that can be mainly classified into two groups: tRFs (tRNA-derived fragments) and tiRNAs (tRNA halves). The abnormal expression of tsRNAs is known to play an important role in the biological progression of breast cancer. However, it's still unclear about the mechanism of tsRNAs in cancer. tRF-1-Ser is a tRF that is high expression in breast cancer and negatively regulated by 25(OH)D. Our study aims to find out the effect of tRF-1-Ser on breast cancer and explore the change of RNA in tRF-1-Ser knock-down breast cancer cells.

2024-05-15 | GSE249937 | GEO

tRNA-derived Small RNAs and their Potential Roles in the Therapeutic Heterogeneity of Sacubitril/valsartan in Heart Failure Patients after Acute Myocardial Infarction

Project description:Background: It has been reported that sacubitril/valsartan can improve cardiac function in acute myocardial infarction (AMI) patients complicated by heart failure (HF). However, a number of patients cannot be treated successfully; this phenomenon is called sacubitril/valsartan resistance (SVR), and the mechanisms remain unclear. Methods:In our present research, the expression profiles of tRNA-derived small RNAs (tsRNAs) in SVR along with NSVR patients were determined by RNA sequencing. Through bioinformatics, qRT–PCR, and cell-based experiments, we identified SVR-related tsRNAs and confirmed their diagnostic value, predicted their targeted genes, and explored the enriched signal pathways as well as regulatory roles of tsRNAs in SVR. Results:Our research indicated that 36 tsRNAs were upregulated and that 21 tsRNAs were downregulated in SVR. Among these tsRNAs, the expression of tRF-59:76-Tyr-GTA-2-M3 and tRF-60:76-Val-AAC-1-M5 was upregulated, while the expression of tRF-1:29-Gly-GCC-1 was downregulated in the group of SVR. Receiver operating characteristic (ROC) curve analysis demonstrated that these three tsRNAs were potential biomarkers of the therapeutic heterogeneity of sacubitril/valsartan. Moreover, tRF-60:76-Val-AAC-1-M5 might target Tnfrsf10b and Bcl2l1 to influence the observed therapeutic heterogeneity through the lipid and atherosclerosis signaling pathways. Conclusions:Hence, tsRNA might play a vital role in SVR. These discoveries provide new insights for the mechanistic investigation of responsiveness to sacubitril/valsartan.

2022-10-19 | GSE207882 | GEO

3'-tRF-CysGCA overexpression alters the expression profile of HEK-293 cells and modulates cellular processes and pathways

Project description:tRNA fragments (tRFs) are small non-coding RNA molecules that are generated through the cleavage of tRNAs and have been implicated in various biological processes. Among the different types of tRFs, the 3′-tRFs have attracted considerable scientific interest due to their regulatory role in gene expression. In this study, we investigated the role of 3′-tRF-CysGCA, a tRF derived from cleavage in the T-loop of tRNACysGCA, in the regulation of gene expression in HEK-293 cells. Previous studies have shown that 3′-tRF-CysGCA is incorporated into the RISC complex and interacts with Argonaute proteins, suggesting its involvement in the regulation of gene expression. However, the general role and effect of the deregulation of 3′-tRF-CysGCA levels in human cells have not been investigated so far. To address this gap, we stably overexpressed 3′-tRF-CysGCA in HEK-293 cells and performed transcriptomics and proteomics experiments. Moreover, we validated the interaction of this tRF with putative targets whose levels were affected after 3′-tRF-CysGCA overexpression. Last, we investigated the implication of 3′-tRF-CysGCA in various pathways using extensive bioinformatics analysis. Our results indicate that 3′-tRF-CysGCA overexpression led to changes in the cell expression profile, and we identified multiple pathways that were affected by the deregulation of this tRF. Additionally, our reporter assays demonstrated that 3′-tRF-CysGCA directly interacted with TMPO and ERGIC1, leading to changes in their expression levels. Taken together, these findings suggest that 3′-tRF-CysGCA plays a significant role in the regulation of gene expression and highlight the potential importance of this tRF in cellular processes.

2023-11-30 | PXD044218 | Pride

A Pilot Study for Protective Roles of tRNA-Derived Small RNA tRF-Ile-AAT-019 in Pathological Progression of Psoriasis

Project description:Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. tRNA-derived small RNA (tsRNA), including tRNA halves and tRNA fragments (tRFs), is a novel class of short non-coding RNA, possessing regulatory functions in many diseases. However, its role in the pathological development of psoriasis has been unknown. In this pilot study, we conducted small RNA sequencing to screen differentially expressed tRFs in psoriatic skin lesions as compared with normal controls. We found 130 upregulated and 104 downregulated tRFs, among which downregulation of tRF-Ile-AAT-019 in psoriatic skin lesions was further confirmed. Bioinformatics analysis by TargetScan and Miranda algorithms revealed that tRF-Ile-AAT-019 might target SERPINE1, thus regulating HIF-1α signaling pathway. We next showed that increased tRF-Ile-AAT-019 could downregulate expressions of SERPINE1, HIF-1α and vascular proliferative markers such as CD34, CD31, Factor VIII, and VEGF, but upregulate expressions of KCs differentiation markers including Keratin1 and Involucrin. Our data suggest that tRF-Ile-AAT-019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1 and blocking HIF-1α signaling pathway, leading to control KCs differentiation and vascular proliferation. This data provides a potential novel targeting pathway for the disease treatment.

2021-02-19 | GSE167057 | GEO

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