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An increasing body of research suggests cancer-induced cardiovascular diseases, leading to the appearance of an interdisciplinary study known as onco-cardiology. Lung cancer has the highest incidence and mortality. Cardiac dysfunction constitutes a major cause of death in lung cancer patients. However, its mechanism has not been elucidated because suitable animal models that adequately mimic clinical features are lacking. Here, we established a novel chemically induced lung cancer mouse model using benzo[a]pyrene and urethane to recapitulate the general characteristics of cardiac dysfunction caused by lung cancer, the cardiac disorders in the context of the progression of lung cancer were evaluated using echocardiographic and histological approaches. The pathological changes included myocardial ischaemia, pericarditis, cardiac pre-cachexia, and pulmonary artery hypertension. We performed sequencing to detect the tRNA-derived fragments and tRNA-derived stress-induced RNAs (tRFs/tiRNAs) expressions in mouse heart tissue. 22 upregulated and 16 downregulated tRFs/tiRNAs were identified. Subsequently, the top 10 significant results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were presented. The in vitro model was established by exposing neonatal rat cardiomyocytes and myocardial fibroblasts to lung tumour cell-conditioned medium, respectively. Western blotting revealed significant changes in cardiac failure markers (atrial natriuretic peptide and α-myosin heavy chain) and cardiac fibrosis markers (Collagen-1 and Collagen-3). Our model adequately reflects the pathological features of lung cancer-induced cardiac dysfunction. Furthermore, the altered tRF/tiRNA profiles showed great promise as novel targets for therapies. These results might pave the way for research on therapeutic targets in onco-cardiology.

Objective: TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are recognized as novel and potential types of non-coding RNAs (ncRNAs), and several tRF/tiRNA signatures are closely associated with tumor diagnosis. This study aimed to analyze the expression profiles of plasma tRFs/tiRNAs and to clarify their diagnostic value in lung adenocarcinoma (LUAD). Methods: The differential expression profiles of plasma tRFs/tiRNAs in patients with four patients with early LUAD, four patients with advanced LUAD, and four healthy controls were analyzed using high-throughput sequencing technology. Then, plasma tRFs/tiRNAs were validated by quantitative realtime polymerase chain reaction (qRT-PCR), and their diagnostic efficiency was appraised by receiver operating characteristic curve analysis. The correlation of candidate plasma tRFs/tiRNAs with clinicopathological features was also analyzed. Finally, bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs/tiRNAs. Results: The sequencing results revealed that tRFs/tiRNAs from plasma samples in patients with LUAD were differently expressed, supporting the necessity of exploring their potential as biomarkers. The validation results of qRT-PCR demonstrated that the expression level of tRF-1:29-Pro-AGG-1-M6 was downregulated in LUAD, while that of tRF-55:76-Tyr-GTA-1-M2 was upregulated, which was consistent with the sequencing data. The areas under the receiver operating characteristic curve of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 were 0.882 and 0.896, respectively, which have significant values in the diagnosis of LUAD. The expressions of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 in LUAD were obviously correlated with various clinicopathological features such as tumor-node-metastasis stage, node stage, and the expression levels of carcinoembryonic antigen. In addition, their expression was significantly altered from before to after tumor resection in LUAD patients. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses further indicated that tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 are widely distributed and apparently enriched in several tumor-related signaling pathways. Conclusions: Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 may be promising components in the development of highly sensitive and noninvasive biomarkers for LUAD diagnosis. [ABSTRACT FROM AUTHOR]

To analyse the expression profiles of serum exosome tRFs/tiRNAs and to explore their diagnostic value in tuberculosis (TB) activity. The serum exosome tRF/tiRNA profile was analysed using high-throughput sequencing technology in 5 active tuberculosis (ATB) patients, 5 latent tuberculosis infection (LTBI) patients and 5 healthy controls (HCs). Then, serum exosome tRFs/tiRNAs were validated by quantitative real-time polymerase chain reaction (qRT–PCR), and their diagnostic value was evaluated by receiver operating characteristic curve (ROC) and area under the curve (AUC). Finally, bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs/tiRNAs. The sequencing results revealed that serum exosome tRF/tiRNA expression profiles were different among ATB patients, LTBI patients and HCs. Three tRFs (tRF-56:75-Trp-CCA-4, tRF-1:22-chrM.Ser-GCT and tRF-56:76-Val-TAC-1-M2) were selected for qRT–PCR validation. The results demonstrated that the expression level of tRF-1-22-chrM.Ser-GCT was upregulated in ATB patients, while tRF-56-75-Trp-CCA-4 was downregulated, which was consistent with the sequencing data. The AUCs of tRF-56:75-Trp-CCA-4 and tRF-1:22-chrM. Ser-GCT were 0.824 and 1.000, respectively, which have significant values in the diagnosis of ATB patients. Moreover, the expression levels of tRF-56:75-Trp-CCA-4 and tRF-1:22-chrM.Ser-GCT and tRF-56:76-Val-TAC-1-M2 in ATB patients and LTBI were different, which indicated that these three tRFs could effectively distinguish ATB patients and LTBI patients. Our findings indicate that serum exosome tRFs can be used as potential markers for the diagnosis of ATB and LTBI. • Systemically identified serum exosome tRF/tiRNA associated with tuberculosis. • Serum exosome tRFs can effectively distinguish ATB from HC and LTBI. • Serum exosome tRFs can be used as potential markers of ATB. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) is one of the most predominant birth defects that causes 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 an abnormal fetal heart and a 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, a 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.

An increasing body of research suggests cancer-induced cardiovascular diseases, leading to the appearance of an interdisciplinary study known as onco-cardiology. Lung cancer has the highest incidence and mortality. Cardiac dysfunction constitutes a major cause of death in lung cancer patients. However, its mechanism has not been elucidated because suitable animal models that adequately mimic clinical features are lacking. Here, we established a novel chemically induced lung cancer mouse model using benzo[ a ]pyrene and urethane to recapitulate the general characteristics of cardiac dysfunction caused by lung cancer, the cardiac disorders in the context of the progression of lung cancer were evaluated using echocardiographic and histological approaches. The pathological changes included myocardial ischaemia, pericarditis, cardiac pre-cachexia, and pulmonary artery hypertension. We performed sequencing to detect the tRNA-derived fragments and tRNA-derived stress-induced RNAs (tRFs/tiRNAs) expressions in mouse heart tissue. 22 upregulated and 16 downregulated tRFs/tiRNAs were identified. Subsequently, the top 10 significant results of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were presented. The in vitro model was established by exposing neonatal rat cardiomyocytes and myocardial fibroblasts to lung tumour cell-conditioned medium, respectively. Western blotting revealed significant changes in cardiac failure markers (atrial natriuretic peptide and α-myosin heavy chain) and cardiac fibrosis markers (Collagen-1 and Collagen-3). Our model adequately reflects the pathological features of lung cancer-induced cardiac dysfunction. Furthermore, the altered tRF/tiRNA profiles showed great promise as novel targets for therapies. These results might pave the way for research on therapeutic targets in onco-cardiology. [Display omitted] ● The combination of urethane and benzo[ a ]pyrene shortened the lung cancer induction phase. ● This model first mimicked the general clinical manifestations of lung cancer-induced cardiac dysfunction. ● The tRNA-derived fragments and tRNA-derived stress-induced RNAs profiles involved were illuminated. ● This model contributes to the discovery of potential therapeutic targets of lung cancer-induced cardiac dysfunction. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) is one of the most predominant birth defects that causes 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 an abnormal fetal heart and a 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, a 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.

Objective: TRNA-derived fragments (tRFs) and tRNA-derived stress-induced RNAs (tiRNAs) are recognized as novel and potential types of non-coding RNAs (ncRNAs), and several tRF/tiRNA signatures are closely associated with tumor diagnosis. This study aimed to analyze the expression profiles of plasma tRFs/tiRNAs and to clarify their diagnostic value in lung adenocarcinoma (LUAD)., Methods: The differential expression profiles of plasma tRFs/tiRNAs in patients with four patients with early LUAD, four patients with advanced LUAD, and four healthy controls were analyzed using high-throughput sequencing technology. Then, plasma tRFs/tiRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR), and their diagnostic efficiency was appraised by receiver operating characteristic curve analysis. The correlation of candidate plasma tRFs/tiRNAs with clinicopathological features was also analyzed. Finally, bioinformatics analysis was performed to explore and identify the potential biological pathways induced by tRFs/tiRNAs., Results: The sequencing results revealed that tRFs/tiRNAs from plasma samples in patients with LUAD were differently expressed, supporting the necessity of exploring their potential as biomarkers. The validation results of qRT-PCR demonstrated that the expression level of tRF-1:29-Pro-AGG-1-M6 was downregulated in LUAD, while that of tRF-55:76-Tyr-GTA-1-M2 was upregulated, which was consistent with the sequencing data. The areas under the receiver operating characteristic curve of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 were 0.882 and 0.896, respectively, which have significant values in the diagnosis of LUAD. The expressions of tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 in LUAD were obviously correlated with various clinicopathological features such as tumor-node-metastasis stage, node stage, and the expression levels of carcinoembryonic antigen. In addition, their expression was significantly altered from before to after tumor resection in LUAD patients. The results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses further indicated that tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 are widely distributed and apparently enriched in several tumor-related signaling pathways., Conclusions: Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 may be promising components in the development of highly sensitive and non-invasive biomarkers for LUAD diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 You, Yang, Wu, Lu, Huang, Chen, Huang, Chen, Xu and Chen.)