tRNA-Derived Fragments as Biomarkers in Bladder Cancer DOI Open Access

Olaf Strømme,

Kathleen A. Heck,

Gaute Brede

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(8), P. 1588 - 1588

Published: April 20, 2024

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying noninvasive biomarkers body fluids such as blood and urine. A source of these biofluids are extracellular vesicles (EVs), nanosized that contain a wide array molecular cargo, including small noncoding RNA transfer RNA-derived fragments (tRF) microRNA. Here, we performed small-RNA next-generation sequencing from EVs urine serum, well serum supernatant. was extracted 15 non-cancer patients (NCPs) benign findings cystoscopy 41 non-muscle BC. Urine were collected before transurethral resection bladder tumors (TUR-b) at routine post-surgery check-ups. We compared levels tRFs pre-surgery samples to NCPs To further verify our findings, 10 stage T1 disease resequenced. When comparing tRF expression between BC NCPs, 14 differentially expressed (DEtRFs) identified. In supernatant, six DEtRFs identified among when four found NCPs. By performing blast search, sequences aligned genomic pertaining processes relevant development, enhancers, regulatory elements CpG islands. Our display number may hold potential for the recurrence-free survival

Language: Английский

Emerging roles of tRNA-derived fragments in cancer DOI Creative Commons
Min Fu, Jianmei Gu,

Maoye Wang

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 13, 2023

Abstract tRNA-derived fragments (tRFs) are an emerging category of small non-coding RNAs that generated from cleavage mature tRNAs or tRNA precursors. The advance in high-throughput sequencing has contributed to the identification increasing number tRFs with critical functions distinct physiological and pathophysiological processes. can regulate cell viability, differentiation, homeostasis through multiple mechanisms thus considered as regulators human diseases including cancer. In addition, evidence suggest extracellular may be utilized promising diagnostic prognostic biomarkers for cancer liquid biopsy. this review, we focus on biogenesis, classification modification tRFs, summarize multifaceted emphasis current research status perspectives

Language: Английский

Citations

62
Emerging Functions for snoRNAs and snoRNA-Derived Fragments DOI Open Access

Maliha Wajahat,

Cameron P. Bracken, Ayla Orang

et al.

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10193 - 10193

Published: Sept. 22, 2021

The widespread implementation of mass sequencing has revealed a diverse landscape small RNAs derived from larger precursors. Whilst many these are likely to be byproducts degradation, there nevertheless metabolically stable fragments tRNAs, rRNAs, snoRNAs, and other non-coding RNA, with number examples the production such being conserved across species. Coupled specific interactions RNA-binding proteins growing experimentally reported suggesting function, case is emerging whereby biological significance extends far beyond miRNAs piRNAs. Related this, similarly complex picture non-canonical roles for precursors, as snoRNAs that also implicated in areas silencing gene expression regulation alternative splicing. This addition body literature describing an additional source miRNA-like regulators. review seeks highlight focusing specifically on "new" them.

Language: Английский

Citations

97
tRNA-derived small RNAs: Mechanisms and potential roles in cancers DOI Creative Commons
Yao Wang, Qiuyan Weng, Jiaxin Ge

et al.

Genes & Diseases, Journal Year: 2022, Volume and Issue: 9(6), P. 1431 - 1442

Published: Jan. 10, 2022

Transfer RNAs (tRNAs) are essential for protein synthesis. Mature or pre-tRNAs may be cleaved to produce tRNA-derived small (tsRNAs). tsRNAs, divided into stress-induced RNA (tiRNAs) and fragments (tRFs), play versatile roles in a number of fundamental biological processes. tsRNAs not only regulatory gene silencing, stability, reverse transcription, translation, but also closely related cell proliferation, migration, cycle, apoptosis. Their abnormal expression is associated with the occurrence development various human diseases, especially cancer. This paper reviews classification, biogenesis, mechanism action research progress date on cancers. These findings provide new opportunities diagnostic biomarkers treatment targets several types cancers including gastric cancer, colorectal hepatocellular carcinomas, pancreatic breast prostate renal carcinoma, ovarian lung bladder thyroid oral leukemia.

Language: Английский

Citations

42
Classification, function, and advances in tsRNA in non-neoplastic diseases DOI Creative Commons

Leah Zhang,

Jie Liu, Yang Hou

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(11)

Published: Nov. 16, 2023

tRNA-derived small RNAs (tsRNAs) are non-coding produced by specific endonucleases following the processing and splicing of precursor or mature tRNAs upon starvation, oxidative stress, hypoxia, other adverse conditions. classified into two major categories, tRNA fragments (tRFs) stress-induced (tiRNAs), based on differences in splice sites. With development high-throughput sequencing technologies recent years, tsRNAs have been found to important biological functions, including inhibition apoptosis, epigenetic regulation, cell-cell communication, translation, regulation gene expression. Additionally, these molecules be aberrantly expressed various diseases involved several pathological processes. In this article, classification nomenclature, potential use as diagnostic biomarkers therapeutic targets non-neoplastic reviewed. Although tsRNA research is at its infancy, their treatment non-tumor warrants further investigation.

Language: Английский

Citations

28
Transfer RNAs as dynamic and critical regulators of cancer progression DOI
Alexandra M. Pinzaru, Sohail F. Tavazoie

Nature reviews. Cancer, Journal Year: 2023, Volume and Issue: 23(11), P. 746 - 761

Published: Oct. 9, 2023

Language: Английский

Citations

25
tRNA-derived fragments: Key determinants of cancer metastasis with emerging therapeutic and diagnostic potentials DOI
Mohammad Salehi, Mohammad Javad Kamali, Aliakbar Rajabzadeh

et al.

Archives of Biochemistry and Biophysics, Journal Year: 2024, Volume and Issue: 753, P. 109930 - 109930

Published: Feb. 16, 2024

Language: Английский

Citations

12
Small RNA‐seq and clinical evaluation of tRNA‐derived fragments in multiple myeloma: Loss of mitochondrial i‐tRFHisGTG results in patients' poor treatment outcome DOI Creative Commons
Konstantinos Soureas, M. Papadimitriou, Panagiotis Malandrakis

et al.

British Journal of Haematology, Journal Year: 2024, Volume and Issue: 204(5), P. 1790 - 1800

Published: Feb. 27, 2024

Summary Despite the substantial progress in multiple myeloma (MM) therapy nowadays, treatment resistance and disease relapse remain major clinical hindrances. Herein, we have investigated tRNA‐derived fragment (tRF) profiles MM precursor stages (smoldering MM/sMM; monoclonal gammopathy of undetermined significance/MGUS), aiming to unveil potential MM‐related tRFs ameliorating prognosis risk stratification. Small RNA‐seq was performed profile bone marrow CD138 + plasma cells, revealing significant deregulation mitochondrial internal tRF HisGTG (mt‐i‐tRF ) versus sMM/MGUS. The screening cohort study consisted 147 patients, mt‐i‐tRF levels were quantified by RT‐qPCR. Disease progression assessed as end‐point for survival analysis, while validation bootstrap decision curve analyses. Screening analysis highlighted potent association reduced with patients' ( p = 0.010), osteolysis 0.023) significantly higher short‐term following first‐line chemotherapy, independently data (HR 1.954; 0.036). Additionally, ‐fitted multivariate models led superior stratification outcome compared disease‐established markers. Notably, our loss a powerful independent indicator post‐treatment leading outcome.

Language: Английский

Citations

9
tRNAGlyGCC-Derived Internal Fragment (i-tRF-GlyGCC) in Ovarian Cancer Treatment Outcome and Progression DOI Open Access
Konstantina Panoutsopoulou, Tobias Dreyer, Julia Dorn

et al.

Cancers, Journal Year: 2021, Volume and Issue: 14(1), P. 24 - 24

Published: Dec. 22, 2021

Epithelial ovarian cancer (EOC) remains a highly-lethal gynecological malignancy, characterized by frequent recurrence, chemotherapy resistance and poor 5-year survival. Identifying novel predictive molecular markers an overdue challenge in the disease's clinical management. Herein, silico analysis of TCGA-OV highlighted tRNA-derived internal fragment (i-tRF-GlyGCC) among most abundant tRFs tumors, while target prediction gene ontology (GO) enrichment predicted its implication key biological processes. Thereafter, i-tRF-GlyGCC levels were quantified screening EOC (n = 98) institutionally-independent serous (SOC) validation cohort 100, OVCAD multicenter study). Disease progression patient death used as endpoints for survival analysis. Internal was performed bootstrap net benefit estimated decision curve The significant association with advanced FIGO stages, suboptimal debulking importantly, early overall patients. corroborated unfavorable value EOC. Ultimately, evaluation established/clinically prognostic offered superior risk-stratification enhanced prognosis. In conclusion, assessment could aid towards personalized prognosis support precision medicine decisions

Language: Английский

Citations

43
tRF-19-W4PU732S promotes breast cancer cell malignant activity by targeting inhibition of RPL27A (ribosomal protein-L27A) DOI Open Access

Zhengxiang Zhang,

Zhi–Ping Liu, Weidong Zhao

et al.

Bioengineered, Journal Year: 2022, Volume and Issue: 13(2), P. 2087 - 2098

Published: Jan. 14, 2022

Breast cancer (BC) is a serious threat to female health. tRNA-derived fragments (tRFs) are popular biomarkers for the diagnosis and treatment of cancer. The purpose this study was identify tRFs related BC explore function regulatory mechanism crucial in cells. Small RNA database used detect tRF profiles from patients controls. Differentially expressed were determined by quantitative reverse transcription PCR (RT-qPCR), evaluated through silence overexpression experiments, target gene investigated luciferase reporter assay, Western blot rescue experiment. We screened tRF-19-W4PU732S, which processed mature tRNA-Ser-AGA, significantly highlyexpressed tissues Inhibition tRF-19-W4PU732S weakened MDA-MB-231 cell proliferation, migration invasion, while enhanced apoptosis. On contrary, promoted MCF-7 whereasreduced Furthermore, induced epithelial-to-mesenchymal transition (EMT) stem-like cells (CSC) phenotypes, such as up-regulation OCT-4A, SOX2 Vimentin down-regulation E-cadherin. Ribosomal protein-L27A (RPL27A) downstream lowly knockdown RPL27A expression partially restored promoting effects on viability, migration, EMT CSC suppression In conclusion, our results manifested that promotes malignant activity inhibiting RPL27A, provides new scientific basis BC.Abbreviations BC: breast cancer; tRNAs: transfer RNAs; tiRNAs: stressinduced tRFs: fragments; CCK-8: Cell Counting Kit-8; PI: propidium iodide; EMT: transition; CSC: cells; RPL27A: ribosomal protein-L27A; RT-qPCR: PCR.

Language: Английский

Citations

29
tRNA-derived fragments (tRFs) in cancer DOI

Yuri Pekarsky,

Veronica Balatti,

Carlo M. Croce

et al.

Journal of Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 17(1), P. 47 - 54

Published: Aug. 29, 2022

Language: Английский

Citations

29