Transfer RNA-Derived Small RNAs: Novel Regulators and Biomarkers of Cancers

Fu, Bi-Fei; Xu, Chaoyang

doi:10.3389/fonc.2022.843598

Cited by 10 publications

(5 citation statements)

References 152 publications

(146 reference statements)

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“…tRF-5s are produced by Dicer cutting the D loop of tRNA; they can be further divided into tRF-5a (14 nt-16 nt), tRF-5b (22 nt-24 nt) and tRF-5c (28 nt-30 nt) ( 4 , 14 ). i-tRFs are derived from the anticodon loop of mature tRNAs and sections of the D-loop and T-loop ( 3 , 14 , 15 ).…”

Section: Biogenesis and Discovery Of Tsrnasmentioning

confidence: 99%

“…Studies have shown that tsRNAs have a wide range of biological functions, including regulating the stability of mRNA, translation regulation, and epigenetic regulation (2)(3)(4)15). The biological functions of tsRNAs are very complex and require further elucidation.…”

Section: Biological Functions Of Tsrnasmentioning

confidence: 99%

“…Transfer RNA-derived small RNAs (tsRNAs) are newly discovered noncoding RNAs (ncRNAs) that were once mistakenly considered random degradation products of transfer RNAs (tRNAs). In recent years, with the development of high-throughput sequencing technology and advances in bioinformatics analysis, tsRNAs have received increasing attention in cancer research ( 2 , 3 ). Based on the specific cleavage at different sites of precursor tRNAs or mature tRNAs, the generated tsRNAs are classified into tRNA-derived stress-induced RNAs (tiRNAs) and tRNA-derived fragments (tRFs).…”

Section: Introductionmentioning

confidence: 99%

“…technology and advances in bioinformatics analysis, tsRNAs have received increasing attention in cancer research (2,3). Based on the specific cleavage at different sites of precursor tRNAs or mature tRNAs, the generated tsRNAs are classified into tRNA-derived stress-induced RNAs (tiRNAs) and tRNA-derived fragments (tRFs).…”

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confidence: 99%

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Transfer RNA-derived small RNAs (tsRNAs) in gastric cancer

2023

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Transfer RNA-derived small RNAs (tsRNAs) are newly discovered noncoding RNAs (ncRNAs). According to the specific cleavage of nucleases at different sites of tRNAs, the produced tsRNAs are divided into tRNA-derived stress-inducible RNAs (tiRNAs) and tRNA-derived fragments (tRFs). tRFs and tiRNAs have essential biological functions, such as mRNA stability regulation, translation regulation and epigenetic regulation, and play significant roles in the occurrence and development of various tumors. Although the roles of tsRNAs in some tumors have been intensively studied, their roles in gastric cancer are still rarely reported. In this review, we focus on recent advances in the generation and classification of tsRNAs, their biological functions, and their roles in gastric cancer. Sixteen articles investigating dysregulated tsRNAs in gastric cancer are summarized. The roles of 17 tsRNAs are summarized, of which 9 were upregulated and 8 were downregulated compared with controls. Aberrant regulation of tsRNAs was closely related to the main clinicopathological factors of gastric cancer, such as lymph node metastasis, Tumor-Node-Metastasis (TNM) stage, tumor size, and vascular invasion. tsRNAs participate in the progression of gastric cancer by regulating the PTEN/PI3K/AKT, MAPK, Wnt, and p53 signaling pathways. The available literature suggests the potential of using tsRNAs as clinical biomarkers for gastric cancer diagnosis and prognosis and as therapeutic targets for gastric cancer treatment.

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Section: Biogenesis and Discovery Of Tsrnasmentioning

confidence: 99%

Section: Biological Functions Of Tsrnasmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Transfer RNA-derived small RNAs (tsRNAs) in gastric cancer

2023

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“…Based on where they cleave from tRNAs, tRFs are divided into four types: tRF-1, tRF-2, tRF-3, and tRF-5. A, B or C subtypes of tRF-5 and tRF-3 can be further categorized ( Yu et al, 2020 ; Fu & Xu, 2022 ). Recent studies have shown that some tRFs may be involved in altering the metabolic pathways underlying breast cancer progression ( Zhu et al, 2021 ; Liu et al, 2022a ).…”

Section: Introductionmentioning

confidence: 99%

tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming

Fu,

Lou,

et al. 2023

Life Sci. Alliance

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tRFs and tiRNAs (tRNA-derived fragments) are an emerging class of small noncoding RNAs produced by the precise shearing of tRNAs in response to specific stimuli. They have been reported to regulate the pathological processes of numerous human cancers. However, the biofunction of tRFs and tiRNAs in the development and progression of papillary thyroid cancer (PTC) has not been reported yet. In this study, we aimed to explore the biological roles of tRFs and tiRNAs in PTC and discovered that a novel 5′tRNA-derived fragment called tRF-1:30-Gly-CCC-3 (tRF-30) was markedly down-regulated in PTC tissues and cell lines. Functionally, tRF-30 inhibited the proliferation and invasion of PTC cells. Mechanistically, tRF-30 directly bound to the biotin-dependent enzyme pyruvate carboxylase (PC), downregulated its protein level, interfered with the TCA cycle intermediate anaplerosis, and thus affected metabolic reprogramming and PTC progression. These findings revealed a novel regulatory mechanism for tRFs and a potential therapeutic target for PTC.

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tRNA modifications and tRNA-derived small RNAs: new insights of tRNA in human disease

Wu,

Li,

Khan

et al. 2024

Cell Biol Toxicol

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tRNAs are codon decoders that convert the transcriptome into the proteome. The field of tRNA research is excited by the increasing discovery of specific tRNA modifications that are installed at specific, evolutionarily conserved positions by a set of specialized tRNA-modifying enzymes and the biogenesis of tRNA-derived regulatory fragments (tsRNAs) which exhibit copious activities through multiple mechanisms. Dysregulation of tRNA modification usually has pathological consequences, a phenomenon referred to as "tRNA modopathy". Current evidence suggests that certain tRNA-modifying enzymes and tsRNAs may serve as promising diagnostic biomarkers and therapeutic targets, particularly for chemoresistant cancers. In this review, we discuss the latest discoveries that elucidate the molecular mechanisms underlying the functions of clinically relevant tRNA modifications and tsRNAs, with a focus on malignancies. We also discuss the therapeutic potential of tRNA/tsRNA-based therapies, aiming to provide insights for the development of innovative therapeutic strategies. Further efforts to unravel the complexities inherent in tRNA biology hold the promise of yielding better biomarkers for the diagnosis and prognosis of diseases, thereby advancing the development of precision medicine for health improvement.

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Transfer RNA-Derived Small RNAs: Novel Regulators and Biomarkers of Cancers

Cited by 10 publications

References 152 publications

Transfer RNA-derived small RNAs (tsRNAs) in gastric cancer

Transfer RNA-derived small RNAs (tsRNAs) in gastric cancer

tRF-1:30-Gly-CCC-3 inhibits thyroid cancer via binding to PC and modulating metabolic reprogramming

tRNA modifications and tRNA-derived small RNAs: new insights of tRNA in human disease

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