Transfer RNA‑derived fragment tRF‑28‑QSZ34KRQ590K in plasma exosomes may be a potential biomarker for atopic dermatitis in pediatric patients

Meng,Li; Jiang,Long; Chen,Jian; Ren,Hongjin; Gao,Zhiqin; Wu,Fei; Wen,Yiyang; Yang,Lianjuan

doi:10.3892/etm.2021.9920

Transfer RNA‑derived fragment tRF‑28‑QSZ34KRQ590K in plasma exosomes may be a potential biomarker for atopic dermatitis in pediatric patients

Authors:
- Li Meng
- Long Jiang
- Jian Chen
- Hongjin Ren
- Zhiqin Gao
- Fei Wu
- Yiyang Wen
- Lianjuan Yang
View Affiliations

Affiliations: Department of Dermatological Mycology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, P.R. China, Department of Dermatological Surgery, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, P.R. China, Department of Dermatological Pathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai 200443, P.R. China
Published online on: March 16, 2021 https://doi.org/10.3892/etm.2021.9920
Article Number: 489

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Atopic dermatitis (AD) is a common chronic relapsing inflammatory disease. There is substantial evidence suggesting that noncoding RNAs have indispensable roles in the pathogenesis of AD. Exosomal transfer RNA‑derived fragments (tRFs) have been identified as potential biomarkers for various disorders. However, the role of tRFs in AD has remained to be elucidated, which was thus the aim of the present study. Plasma samples from 23 pediatric patients with AD and 23 healthy controls were collected. Exosomes were successfully isolated from plasma according to the manufacturer's protocol. Small RNA sequencing was performed in 3 patients with AD and 3 controls, and 135 significantly differentially expressed plasma exosomal tRFs were identified, including 36 upregulated and 99 downregulated tRFs. Using the miRanda and RNAhybrid databases, 58,227 target genes of these 135 differentially expressed tRFs were predicted. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that these target genes of tRFs are involved in multiple functions and pathways associated with AD. Downregulation of tRF‑28‑QSZ34KRQ590K and tRF‑33‑Q99P9P9NH57SD3 were validated in 20 patients with AD and 20 controls by reverse transcription‑quantitative PCR and tRF‑28‑QSZ34KRQ590K exhibited significance in the receiver operating characteristic curve analysis. The present study was the first to provide a tRF profile in AD and implied that plasma exosomal tRF‑28‑QSZ34KRQ590K may be a potential biomarker for pediatric patients with AD. The present study enhanced the understanding of the pathogenesis of AD and provided a novel marker for the diagnosis and targeted treatment of AD.

View Figures

View References

1	Abrams EM and Sicherer S: Cutaneous sensitization to peanut in children with atopic dermatitis: A window to prevention of peanut allergy. JAMA Dermatol. 155:13–14. 2018.PubMed/NCBI View Article : Google Scholar
2	Bin L and Leung DY: Genetic and epigenetic studies of atopic dermatitis. Allergy Asthma Clin Immunol. 12(52)2016.PubMed/NCBI View Article : Google Scholar
3	Guescini M, Genedani S, Stocchi V and Agnati LF: Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J Neural Transm (Vienna). 117:1–4. 2010.PubMed/NCBI View Article : Google Scholar
4	Miranda KC, Bond DT, McKee M, Skog J, Paunescu TG, Da Silva N, Brown D and Russo LM: Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease. Kidney Int. 78:191–199. 2010.PubMed/NCBI View Article : Google Scholar
5	Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ and Lotvall JO: Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 9:654–659. 2007.PubMed/NCBI View Article : Google Scholar
6	Kumar P, Kuscu C and Dutta A: Biogenesis and function of transfer RNA-related fragments (tRFs). Trends Biochem Sci. 41:679–689. 2016.PubMed/NCBI View Article : Google Scholar
7	Ruggero K, Guffanti A, Corradin A, Sharma VK, De Bellis G, Corti G, Grassi A, Zanovello P, Bronte V, Ciminale V and D'Agostino DM: Small noncoding RNAs in cells transformed by human T-cell leukemia virus type 1: A role for a tRNA fragment as a primer for reverse transcriptase. J Virol. 88:3612–3622. 2014.PubMed/NCBI View Article : Google Scholar
8	Yeung ML, Bennasser Y, Watashi K, Le SY, Houzet L and Jeang KT: Pyrosequencing of small non-coding RNAs in HIV-1 infected cells: Evidence for the processing of a viral-cellular double-stranded RNA hybrid. Nucleic Acids Res. 37:6575–6586. 2009.PubMed/NCBI View Article : Google Scholar
9	Guo Y, Bosompem A, Mohan S, Erdogan B, Ye F, Vickers KC, Sheng Q, Zhao S, Li CI, Su PF, et al: Transfer RNA detection by small RNA deep sequencing and disease association with myelodysplastic syndromes. BMC Genomics. 16(727)2015.PubMed/NCBI View Article : Google Scholar
10	Martens-Uzunova ES, Jalava SE, Dits NF, van Leenders GJ, Moller S, Trapman J, Bangma CH, Litman T, Visakorpi T and Jenster G: Diagnostic and prognostic signatures from the small non-coding RNA transcriptome in prostate cancer. Oncogene. 31:978–991. 2012.PubMed/NCBI View Article : Google Scholar
11	Victoria Martinez B, Dhahbi JM, Nunez Lopez YO, Lamperska K, Golusinski P, Luczewski L, Kolenda T, Atamna H, Spindler SR, Golusinski W and Masternak MM: Circulating small non-coding RNA signature in head and neck squamous cell carcinoma. Oncotarget. 6:19246–19263. 2015.PubMed/NCBI View Article : Google Scholar
12	Kumar P, Mudunuri SB, Anaya J and Dutta A: tRFdb: A database for transfer RNA fragments. Nucleic Acids Res. 43:D141–D145. 2015.PubMed/NCBI View Article : Google Scholar
13	Thompson DM and Parker R: Stressing out over tRNA cleavage. Cell. 138:215–219. 2009.PubMed/NCBI View Article : Google Scholar
14	Lee YS, Shibata Y, Malhotra A and Dutta A: A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 23:2639–2649. 2009.PubMed/NCBI View Article : Google Scholar
15	Goodarzi H, Liu X, Nguyen HC, Zhang S, Fish L and Tavazoie SF: Endogenous tRNA-derived fragments suppress breast cancer progression via YBX1 displacement. Cell. 161:790–802. 2015.PubMed/NCBI View Article : Google Scholar
16	Rajka G and Hanifin JM: Diagnostic features of atopic dermatitis. Acta Dermato-venereologica. 60:44–47. 1980.
17	Severity scoring of atopic dermatitis. The SCORAD index. Consensus report of the European task force on atopic dermatitis. Dermatology. 186:23–31. 1993.PubMed/NCBI View Article : Google Scholar
18	Zhang L, Liu S, Wang JH, Zou J, Zeng H, Zhao H, Zhang B, He Y, Shi J, Yoshida S and Zhou Y: Differential expressions of microRNAs and transfer RNA-derived Small RNAs: Potential targets of choroidal neovascularization. Curr Eye Res. 44:1226–1235. 2019.PubMed/NCBI View Article : Google Scholar
19	Mazzei M, Vascellari M, Zanardello C, Melchiotti E, Vannini S, Forzan M, Marchetti V, Albanese F and Abramo F: Quantitative real time polymerase chain reaction (qRT-PCR) and RNAscope in situ hybridization (RNA-ISH) as effective tools to diagnose feline herpesvirus-1-associated dermatitis. Vet Dermatol. 30:e491–e147. 2019.PubMed/NCBI View Article : Google Scholar
20	Shen Y, Yu X, Zhu L, Li T, Yan Z and Guo J: Transfer RNA-derived fragments and tRNA halves: Biogenesis, biological functions and their roles in diseases. J Mol Med. 96:1167–1176. 2018.PubMed/NCBI View Article : Google Scholar
21	Soares AR and Santos M: Discovery and function of transfer RNA-derived fragments and their role in disease. Wiley Interdiscip Rev RNA: 8, 2017 doi: 10.1002/wrna.1423.
22	Zhang Z, Xiao C, Gibson AM, Bass SA and Khurana Hershey GK: EGFR signaling blunts allergen-induced IL-6 production and Th17 responses in the skin and attenuates development and relapse of atopic dermatitis. J Immunol. 192:859–866. 2014.PubMed/NCBI View Article : Google Scholar
23	Wu A, Chen H, Xu C, Zhou J, Chen S, Shi Y, Xu J, Gan J and Zhang J: miR-203a is involved in HBx-induced inflammation by targeting Rap1a. Exp Cell Res. 349:191–197. 2016.PubMed/NCBI View Article : Google Scholar
24	Kyriakis JM and Avruch J: Mammalian MAPK signal transduction pathways activated by stress and inflammation: A 10-year update. Physiol Rev. 92:689–737. 2012.PubMed/NCBI View Article : Google Scholar
25	Hirota T, Takahashi A, Kubo M, Tsunoda T, Tomita K, Sakashita M, Yamada T, Fujieda S, Tanaka S, Doi S, et al: Genome-wide association study identifies eight new susceptibility loci for atopic dermatitis in the Japanese population. Nat Genet. 44:1222–1226. 2012.PubMed/NCBI View Article : Google Scholar
26	Chen CP, Lin SP, Chern SR, Tsai FJ, Wu PC, Lee CC, Chen YT, Chen WL and Wang W: A de novo 7.9 Mb deletion in 22q13.2→qter in a boy with autistic features, epilepsy, developmental delay, atopic dermatitis and abnormal immunological findings. Eur J Med Genet. 53:329–332. 2010.PubMed/NCBI View Article : Google Scholar