Screening and potential role of tRFs and tiRNAs derived from tRNAs in the carcinogenesis and development of lung adenocarcinoma

Zhang, Jinhua; Li, Linhui; Luo, Lilin; Xiao-ling, Yang; Zhang, Juanjuan; Xie, Yuxin; Liang, Rui; Wang, Wanpu; Lu, Shuaiyao

doi:10.3892/ol.2021.12767

Cited by 12 publications

(6 citation statements)

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“…There has been an increase in the incidence of lung adenocarcinoma in recent years, and despite using a variety of treatment methods, the mortality rate remains high 14 . Moreover, LUAD has a poor prognosis and inadequate screening methods, which result in a low clinical cure rate 15 . Therefore, a novel biomarker must be developed to predict the prognosis of LUAD and provide treatment targets.…”

Section: Discussionmentioning

confidence: 99%

Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

Niu

Zhao

et al. 2022

Sci Rep

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Lung adenocarcinoma (LUAD) is one of the most universal types of cancer all over the world and its morbidity continues to rise year by year. Growing evidence has demonstrated that endoplasmic reticulum stress is highly activated in cancer cells and plays a key role in regulating the fate of cancer cells. However, the role and mechanism of endoplasmic reticulum stress in lung adenocarcinoma genesis and development remains unclear. In this research, we developed a prognostic model to predict the overall survival of patients with LUAD utilizing endoplasmic reticulum stress-related genes and screened out potential small molecular compounds, which could assist the clinician in making accurate decisions and better treat LUAD patients. Firstly, we downloaded 419 endoplasmic reticulum stress-related genes (ERSRGs) from Molecular Signatures Database (MSigDB). Secondly, we obtained information about the transcriptome profiling and corresponding clinical data of 59 normal samples and 535 lung adenocarcinoma samples from The Cancer Genome Atlas (TCGA) database. Next, we used the DESeq2 package to identify differentially expressed genes related to endoplasmic reticulum stress. We performed univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analysis to establish a prognostic model for LUAD patients based on ERSRGs. Then, we carried out univariate and multivariate independent prognostic analysis of endoplasmic reticulum stress-related gene (ERSRG) score and some clinical traits of lung adenocarcinoma. Additionally, we developed a clinically applicable nomogram for predicting survival for LUAD patients over one, three, and five years. Moreover, we carried out a drug sensitivity analysis to identify novel small molecule compounds for LUAD treatment. Finally, we examined the tumor microenvironment (TME) and immune cell infiltrating analysis to explore the interactions between immune and cancer cells. 142 differentially expressed ERSRGs were identified by using the DESeq2 package. A prognostic model was built based on 7 differentially expressed ERSRGs after performing univariate Cox regression, LASSO regression, and multivariate Cox regression analysis. According to the results of univariate and multivariate independent prognostic analysis, we found ERSRG score can be used as an independent prognostic maker. Using the Kaplan–Meier curves, we found low-risk patients had higher survival probability than high-risk patients in both training set and test set. A nomogram was drawn to predict 1-, 3-, and 5-year survival probability. The calibration curves explained good performance of the model for the prediction of survival. Phenformin, OSU-03012, GSK-650394 and KIN001-135 were identified as the drugs most likely to provide important information to clinicians about the treatment of LUAD patients. A prognostic prediction model was established based on 7 differentially expressed ERSRGs (PDX1, IGFBP1, DDIT4, PPP1R3G, CFTR, DERL3 and NUPR1), which could effectively predict the prognosis of LUAD patients and give a reference for clinical doctors to help LUAD patients to make better treatment tactics. Based on the 4 small molecule compounds (Phenformin, OSU-03012, GSK-650394 and KIN001-135) we discovered, targeting endoplasmic reticulum stress-related genes may also be a therapeutic approach for LUAD patients.

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Section: Discussionmentioning

confidence: 99%

Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

Niu

Zhao

et al. 2022

Sci Rep

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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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“…Further analysis also found that the isoforms corresponding to the missing tRNA isodecoders Arg-TCT, Leu-TAA, Phe-GAA, and Ser-CGA in the control group were tRF-1, tRF-3a, tRF-3b, and tRF-5a, which are overexpressed in LUAD. Studies have previously assessed the presence of differentially expressed tRFs/tiRNAs in LUAD tissue samples ( 25 – 27 ). This study revealed the altered tRF/tiRNA expression in the plasma samples of LUAD patients from another perspective, thus also providing support for exploring tRFs/tiRNAs as potential biomarkers for LUAD.…”

Section: Discussionmentioning

confidence: 99%

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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Screening and potential role of tRFs and tiRNAs derived from tRNAs in the carcinogenesis and development of lung adenocarcinoma

Cited by 12 publications

References 50 publications

Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

Construction and validation of a prognostic model for lung adenocarcinoma based on endoplasmic reticulum stress-related genes

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

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

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