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tRNA-derived fragments: mechanism of gene regulation and clinical application in lung cancer

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Abstract

Lung cancer, being the most widespread and lethal form of cancer globally, has a high incidence and mortality rate primarily attributed to challenges associated with early detection, extensive metastasis, and frequent recurrence. In the context of lung cancer development, noncoding RNA molecules have a crucial role in governing gene expression and protein synthesis. Specifically, tRNA-derived fragments (tRFs), a subset of noncoding RNAs, exert significant biological influences on cancer progression, encompassing transcription and translation processes as well as epigenetic regulation. This article primarily examines the mechanisms by which tRFs modulate gene expression and contribute to tumorigenesis in lung cancer. Furthermore, we provide a comprehensive overview of the current bioinformatics analysis of tRFs in lung cancer, with the objective of offering a systematic and efficient approach for studying the expression profiling, functional enrichment, and molecular mechanisms of tRFs in this disease. Finally, we discuss the clinical significance and potential avenues for future research on tRFs in lung cancer. This paper presents a comprehensive systematic review of the existing research findings on tRFs in lung cancer, aiming to offer improved biomarkers and drug targets for clinical management of lung cancer.

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Abbreviations

ψ:

pseudouracil

3’-UTR:

3’-untranslated region

AGO:

Argonaute

ALKBH3:

AlkB homologue 3

ANG:

Angiogenin

AKT:

Protein kinase B

AURKA:

Aurora kinase A

BCL2L11:

B-cell lymphoma 2-like 11

CELF6:

CUGBP Elav-Like Family Member 6

ceRNA:

Competitive endogenous RNA

circRNAs:

Circular RNAs

D:

Dihydrouracil

EGFR-TKIs:

Epidermal growth factor receptor tyrosine kinase inhib-itors

ELK4:

ETS-like transcription factor 4

EMT:

Epithelial-mesenchymal transition

GADD45G:

DNA damage 45G

GEPIA:

Gene Expression Profiling Interactive Analysis

GEO:

Gene Expression Omnibus

Gm:

2’-O-methylguanosine

GO:

Gene Ontology

GSEA:

Gene set enrichment analysis

H3K27ac:

H3-lysine-27-acetylation

H3K4me1:

H3-lysine 4-monomethylation

HSPB1:

Small heat shock protein-1

i6A:

N6-isopentenyl adenosine

IGF1R:

Insulin-like growth factor 1 receptor

KEGG:

Kyoto Encyclopedia of Genes and Genomes

LARS1:

Leucine-tRNA synthetase

lncRNAs:

Long noncoding RNAs

LUAD:

Lung adenocarcinoma

LUSC:

lung squamous cell carcinoma

MED29:

Mediator complex subunit 29

miRNAs:

MicroRNAs

Mthfd1l:

Methylenetetra-hydrofolate dehydrogenase 1 like

ncRNAs:

Noncoding RNAs

NSun2:

NOP2/Sun RNA methyltransferase 2

NSCLC:

Non-small cell lung cancer

Pafah1b1:

Platelet-activating factor acetylhydrolase 1 beta 1

PIWIL2:

Piwi-like protein 2

RBPs:

RNA-binding proteins

RIP:

RNA immunoprecipitation

RISC:

RNA-induced silencing complex

RNP:

Ribonucleoprotein

RUNX1:

Runt-related transcription factor 1

SCLC:

Small cell lung cancer

SPRY4:

Sprouty 4

TCGA:

The Cancer Genome Atlas

TEM:

Transmission electron microscopy

TFs:

Transcription factors

tiRNAs:

tRNA semimolecules

tRFs:

tRNA-derived fragments

TRMT2A:

tRNA methyltransferase 2 homologue A

YTHDF1:

YTH N6-methyladenosine RNA binding protein 1

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Acknowledgements

The authors are thankful for the Shanghai Science and Technology Committee (No. 20S11901300) and Yunnan Provincial Science and Technology Department - Kunming Medical University Joint Fund Key Project (202201AY070001-137). The authors are thankful for Shanghai University for providing open access support. The authors thank Dr. Yang Shao (Cancer Institute, Fudan University Shanghai Cancer Center) for critical reading of the manuscript.

Funding

This study was funded by the Shanghai Science and Technology Committee (No. 20S11901300) and Yunnan Provincial Science and Technology Department - Kunming Medical University Joint Fund Key Project (202201AY070001-137). Open access funding was provided by Shanghai University.

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Authors and Affiliations

  1. Lab for Noncoding RNA & Cancer, School of Life Sciences, Shanghai University, 381 Nanchen Road, Shanghai, 200444, China

    Fan Wu, Qianqian Yang, Wei Pan, Wei Meng & Zhongliang Ma

  2. Department of Thoracic Surgery, The Third Affiliated Hospital of Kunming Medical University, Cancer Hospital, Yunnan Cancer Center, Kunming, 650118, China

    Weiwei Wang

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  1. Fan Wu
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Contributions

Zhongliang Ma, Weiwei Wang, Fan Wu presented conceptualization. Qianqian Yang, Wei Pan, Wei Meng searched literatures. Fan Wu wrote the main manuscript text. Fan Wu, QianqianYang, Wei Pan, Wei Meng prepared figures and tables. Zhongliang Ma, Weiwei Wang supervised the review. All authors reviewed the manuscript.

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Wu, F., Yang, Q., Pan, W. et al. tRNA-derived fragments: mechanism of gene regulation and clinical application in lung cancer. Cell Oncol. 47, 37–54 (2024). https://doi.org/10.1007/s13402-023-00864-z

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