A novel tRNA-derived fragment AS-tDR-007333 promotes the malignancy of NSCLC via the HSPB1/MED29 and ELK4/MED29 axes

Yang, Wenjing; Gao, Kaiping; Yu, Qian; Huang, Yongyi; Qin, Xiang; Chen, Cheng; Chen, Qianqian; Wang, Yiling; Fang, Feng; He, Qihan; Chen, Siqi; Xiong, Juan; Chen, Yangchao; Xie, Ni; Zheng, Duo; Zhai, Rihong

doi:10.1186/s13045-022-01270-y

Cited by 50 publications

(37 citation statements)

References 43 publications

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“…measured plasma AS-tDR-007333 levels and found that they were significantly higher in NSCLC patients than in healthy controls. The study further revealed that the AUC for AS-tDR-007333 was 0.9379, which suggests that AS-tDR-007333 can serve as a diagnostic biomarker for NSCLC ( 28 ). Enlightened by previous research carried out by Yang et al., we screened and identified tRF-55:76-Tyr-GTA-1-M2 and tRF-1:29-Pro-AGG-1-M6 as potential biomarkers with high diagnostic sensitivity and specificity in LUAD patients.…”

Section: Discussionmentioning

confidence: 85%

Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 as novel diagnostic biomarkers for lung adenocarcinoma

You

Yang

Wu³

et al. 2022

Front. Oncol.

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ObjectiveTRNA-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).MethodsThe 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.ResultsThe 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.ConclusionsPlasma 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.

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Section: Discussionmentioning

confidence: 85%

Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 as novel diagnostic biomarkers for lung adenocarcinoma

You

Yang

Wu³

et al. 2022

Front. Oncol.

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“…In this study, we find that tRF-5c were the most abundant categories in pig spleen. Previous studies showed that the class of tsRNA in stomach [ 59 ], lung [ 60 ] and plasma [ 61 ] were mainly tRF-5c. However, other results were also reported tiRNAs were primarily observed in ovary [ 62 ] and thyroid [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of tRNA-Derived Small RNAs and microRNAs Associated with Immunocompromise in an Intrauterine Growth-Restricted Pig Model

Gan

Chen

et al. 2022

Animals

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Intrauterine growth restriction (IUGR) is an important cause of newborn morbidity and mortality in mammals. Transfer RNA-derived small RNA (tsRNA) has become an emerging non-coding RNA in recent years. tsRNA and microRNAs (miRNAs) share similar mechanisms, which are involved in various biological processes. In this study, the pig was used as a model of IUGR, and the tsRNA and miRNA expression profile in the spleen was characterized by RNA sequencing. A total of 361 miRNAs and 620 tsRNAs were identified, of which 22 were differentially expressed miRNA (DEM) and 25 differentially expressed tsRNA (DET). tRF-5c were the primary tsRNA type making up more than 90%, and the most abundantly expressed tsRNAs are from tRNA-Gly-GCC. Functional enrichment analysis found that those DETs and DEMs have been implicated in the immune system process. Protein–protein interaction (PPI) network analysis revealed ssc-miR-370, ssc-miR-206, tiRNA-Ser-TGA-001 and tRF-Val-AAC-034 could be major regulators. TNF, TLR4, CD44, MAPK1 and STAT1 were predicted hub target genes. Those DETs and DEMs may regulate the T-cell receptor signaling pathway and Toll-like receptor signaling pathway to mediate the immunocompromise caused by IUGR. The results discussed in this article uncover the potential role of tsRNAs and miRNAs in IUGR porcine spleen.

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“…The results indicate the potential value of tRFs as therapeutic agents (98). In the context of oncogenic tRFs, the inhibition of certain tRFs may have therapeutic effects on cancer (99). Yang et al demonstrated that upregulation of AS-tDR-007333 significantly promoted the growth and migration of non-small cell lung cancer cells (99).…”

Section: Trfs As Therapeutic Agents or Targets For Cancer Therapymentioning

confidence: 98%

“…In the context of oncogenic tRFs, the inhibition of certain tRFs may have therapeutic effects on cancer (99). Yang et al demonstrated that upregulation of AS-tDR-007333 significantly promoted the growth and migration of non-small cell lung cancer cells (99). A mechanistic study revealed that AS-tDR-007333 and HSPB1 synergistically enhance transcription of mediator complex subunit 29 (MED29) by modifying histone modifications on MED29 promoter regions.…”

Section: Trfs As Therapeutic Agents or Targets For Cancer Therapymentioning

confidence: 99%

tRNA derived fragments:A novel player in gene regulation and applications in cancer

Zhang

Yu²,

Xie³

et al. 2023

Front. Oncol.

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The heterogeneous species of tRNA-derived fragments (tRFs) with specific biological functions was recently identified. Distinct roles of tRFs in tumor development and viral infection, mediated through transcriptional and post-transcriptional regulation, has been demonstrated. In this review, we briefly summarize the current literatures on the classification of tRFs and the effects of tRNA modification on tRF biogenesis. Moreover, we highlight the tRF repertoire of biological roles such as gene silencing, and regulation of translation, cell apoptosis, and epigenetics. We also summarize the biological roles of various tRFs in cancer development and viral infection, their potential value as diagnostic and prognostic biomarkers for different types of cancers, and their potential use in cancer therapy.

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A novel tRNA-derived fragment AS-tDR-007333 promotes the malignancy of NSCLC via the HSPB1/MED29 and ELK4/MED29 axes

Cited by 50 publications

References 43 publications

Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 as novel diagnostic biomarkers for lung adenocarcinoma

Plasma tRF-1:29-Pro-AGG-1-M6 and tRF-55:76-Tyr-GTA-1-M2 as novel diagnostic biomarkers for lung adenocarcinoma

Characteristics of tRNA-Derived Small RNAs and microRNAs Associated with Immunocompromise in an Intrauterine Growth-Restricted Pig Model

tRNA derived fragments:A novel player in gene regulation and applications in cancer

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