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Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant

Acute rejection (AR) is a common and grave complication of liver transplantation (LT). The diagnosis of AR is challenging because it has nonspecific clinical features and requires invasive procedures. Since extracellular vesicles (EVs) are promising candidates as indicators for diagnosis of various...

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Autores principales: Wang, Wenjing, Li, Wen, Cao, Li, Wang, Bo, Liu, Chang, Qin, Yannan, Guo, Bo, Huang, Chen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606588/
https://www.ncbi.nlm.nih.gov/pubmed/36313425
http://dx.doi.org/10.3389/fgene.2022.1015049
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author Wang, Wenjing
Li, Wen
Cao, Li
Wang, Bo
Liu, Chang
Qin, Yannan
Guo, Bo
Huang, Chen
author_facet Wang, Wenjing
Li, Wen
Cao, Li
Wang, Bo
Liu, Chang
Qin, Yannan
Guo, Bo
Huang, Chen
author_sort Wang, Wenjing
collection PubMed
description Acute rejection (AR) is a common and grave complication of liver transplantation (LT). The diagnosis of AR is challenging because it has nonspecific clinical features and requires invasive procedures. Since extracellular vesicles (EVs) are promising candidates as indicators for diagnosis of various diseases, this study aimed to identify serum EV microRNAs (miRNAs) as potential biomarkers for AR in patients subjected to LT. We collected clinical information and serum samples from the liver transplant recipients with and without AR (non-AR). EVs from the serum were isolated via ultracentrifugation and identified using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. EV RNA was extracted and sequenced on an Illumina HiSeq 2500/2000 platform to identify differentially expressed miRNAs between the groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the target gene candidates of the differentially expressed miRNAs to test their functions in biological systems. Then, we validated 12 differentially expressed miRNAs by quantitative real-time PCR. The results demonstrated that 614 EV miRNAs were significantly altered (387 up regulated and 227 down regulated) between non-AR and AR patients. GO enrichment analysis revealed that these target genes were related to cellular processes, single-organism processes, biological regulation, metabolic processes, cells, cell parts, protein-binding processes, nucleoid binding, and catalytic activity. Furthermore, KEGG pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were primarily involved in ubiquitin-mediated proteolysis, lysosomes, and protein processing in the endoplasmic reticulum. miR-223 and let-7e-5p in AR patients were significantly up-regulated compared to those in non-AR patients, whereas miR-199a-3p was significantly down-regulated, which was consistent with sequencing results. The expression of serum EV miRNAs (up-regulated: miR-223 and let-7e-5p and miR-486-3p; down regulated: miR-199a-3p, miR-148a-3p and miR-152-3p) in AR patients was significantly different from that in non-AR patients, and these miRNAs can serve as promising diagnostic biomarkers for AR in patients subjected to liver transplant.
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spelling pubmed-96065882022-10-28 Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant Wang, Wenjing Li, Wen Cao, Li Wang, Bo Liu, Chang Qin, Yannan Guo, Bo Huang, Chen Front Genet Genetics Acute rejection (AR) is a common and grave complication of liver transplantation (LT). The diagnosis of AR is challenging because it has nonspecific clinical features and requires invasive procedures. Since extracellular vesicles (EVs) are promising candidates as indicators for diagnosis of various diseases, this study aimed to identify serum EV microRNAs (miRNAs) as potential biomarkers for AR in patients subjected to LT. We collected clinical information and serum samples from the liver transplant recipients with and without AR (non-AR). EVs from the serum were isolated via ultracentrifugation and identified using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. EV RNA was extracted and sequenced on an Illumina HiSeq 2500/2000 platform to identify differentially expressed miRNAs between the groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on the target gene candidates of the differentially expressed miRNAs to test their functions in biological systems. Then, we validated 12 differentially expressed miRNAs by quantitative real-time PCR. The results demonstrated that 614 EV miRNAs were significantly altered (387 up regulated and 227 down regulated) between non-AR and AR patients. GO enrichment analysis revealed that these target genes were related to cellular processes, single-organism processes, biological regulation, metabolic processes, cells, cell parts, protein-binding processes, nucleoid binding, and catalytic activity. Furthermore, KEGG pathway analysis demonstrated that the target genes of the differentially expressed miRNAs were primarily involved in ubiquitin-mediated proteolysis, lysosomes, and protein processing in the endoplasmic reticulum. miR-223 and let-7e-5p in AR patients were significantly up-regulated compared to those in non-AR patients, whereas miR-199a-3p was significantly down-regulated, which was consistent with sequencing results. The expression of serum EV miRNAs (up-regulated: miR-223 and let-7e-5p and miR-486-3p; down regulated: miR-199a-3p, miR-148a-3p and miR-152-3p) in AR patients was significantly different from that in non-AR patients, and these miRNAs can serve as promising diagnostic biomarkers for AR in patients subjected to liver transplant. Frontiers Media S.A. 2022-10-13 /pmc/articles/PMC9606588/ /pubmed/36313425 http://dx.doi.org/10.3389/fgene.2022.1015049 Text en Copyright © 2022 Wang, Li, Cao, Wang, Liu, Qin, Guo and Huang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Wang, Wenjing
Li, Wen
Cao, Li
Wang, Bo
Liu, Chang
Qin, Yannan
Guo, Bo
Huang, Chen
Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant
title Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant
title_full Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant
title_fullStr Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant
title_full_unstemmed Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant
title_short Serum extracellular vesicle MicroRNAs as candidate biomarkers for acute rejection in patients subjected to liver transplant
title_sort serum extracellular vesicle micrornas as candidate biomarkers for acute rejection in patients subjected to liver transplant
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606588/
https://www.ncbi.nlm.nih.gov/pubmed/36313425
http://dx.doi.org/10.3389/fgene.2022.1015049
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