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Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals
BACKGROUND: Frailty is an intermediate and reversible geriatric syndrome that often precedes dependence. Therefore, its identification is essential to prevent dependence. Several molecules have been proposed as biomarkers of frailty, but none of them have reached clinical practice. Recently, circula...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334614/ https://www.ncbi.nlm.nih.gov/pubmed/37434183 http://dx.doi.org/10.1186/s12979-023-00356-6 |
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author | Iparraguirre, Leire Alberro, Ainhoa Iñiguez, Saioa GS Muñoz-Culla, Maider Vergara, Itziar Matheu, Ander Otaegui, David |
author_facet | Iparraguirre, Leire Alberro, Ainhoa Iñiguez, Saioa GS Muñoz-Culla, Maider Vergara, Itziar Matheu, Ander Otaegui, David |
author_sort | Iparraguirre, Leire |
collection | PubMed |
description | BACKGROUND: Frailty is an intermediate and reversible geriatric syndrome that often precedes dependence. Therefore, its identification is essential to prevent dependence. Several molecules have been proposed as biomarkers of frailty, but none of them have reached clinical practice. Recently, circular RNAs have emerged as new non-coding RNAs. Their regulatory role together with their high stability in biofluids makes them good candidates as biomarkers for various processes, but, to date, no study has characterized the expression of circRNA in frailty. RESULTS: We studied RNA from leukocytes of 35 frails and 35 robust individuals. After RNA-Sequencing, circRNA detection was performed by CIRI2 and Circexplorer2 and differential expression analysis by DESeq2. Validation was performed by Quantitative-PCR. Linear Discriminant Analysis was performed to determine the best circRNA combination to discriminate frail from robust. In addition, CircRNA candidates were studied in 13 additional elder donors before and after a 3-month physical intervention. We found 89 differentially expressed circRNAs (p-value<0.05, FC>|1.5|) with frailty. Upregulation of hsa_circ_0007817, hsa_circ_0101802 and hsa_circ_0060527 in frail individuals was validated. The combination of hsa_circ_0079284, hsa_circ_0007817 and hsa_circ_0075737 levels showed a great biomarker value with a 95.9% probability of correctly classifying frail and robust individuals. Moreover, hsa_circ_0079284 levels decreased after physical intervention in concordance with an improvement in frailty scores. CONCLUSIONS: This work describes for the first time a different expression pattern of circular RNA (circRNAs) between frail and robust individuals. Moreover, the level of some circRNAs is modulated after a physical intervention. These results suggest that they could be used as minimally invasive biomarkers of frailty. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-023-00356-6. |
format | Online Article Text |
id | pubmed-10334614 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-103346142023-07-12 Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals Iparraguirre, Leire Alberro, Ainhoa Iñiguez, Saioa GS Muñoz-Culla, Maider Vergara, Itziar Matheu, Ander Otaegui, David Immun Ageing Research BACKGROUND: Frailty is an intermediate and reversible geriatric syndrome that often precedes dependence. Therefore, its identification is essential to prevent dependence. Several molecules have been proposed as biomarkers of frailty, but none of them have reached clinical practice. Recently, circular RNAs have emerged as new non-coding RNAs. Their regulatory role together with their high stability in biofluids makes them good candidates as biomarkers for various processes, but, to date, no study has characterized the expression of circRNA in frailty. RESULTS: We studied RNA from leukocytes of 35 frails and 35 robust individuals. After RNA-Sequencing, circRNA detection was performed by CIRI2 and Circexplorer2 and differential expression analysis by DESeq2. Validation was performed by Quantitative-PCR. Linear Discriminant Analysis was performed to determine the best circRNA combination to discriminate frail from robust. In addition, CircRNA candidates were studied in 13 additional elder donors before and after a 3-month physical intervention. We found 89 differentially expressed circRNAs (p-value<0.05, FC>|1.5|) with frailty. Upregulation of hsa_circ_0007817, hsa_circ_0101802 and hsa_circ_0060527 in frail individuals was validated. The combination of hsa_circ_0079284, hsa_circ_0007817 and hsa_circ_0075737 levels showed a great biomarker value with a 95.9% probability of correctly classifying frail and robust individuals. Moreover, hsa_circ_0079284 levels decreased after physical intervention in concordance with an improvement in frailty scores. CONCLUSIONS: This work describes for the first time a different expression pattern of circular RNA (circRNAs) between frail and robust individuals. Moreover, the level of some circRNAs is modulated after a physical intervention. These results suggest that they could be used as minimally invasive biomarkers of frailty. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12979-023-00356-6. BioMed Central 2023-07-11 /pmc/articles/PMC10334614/ /pubmed/37434183 http://dx.doi.org/10.1186/s12979-023-00356-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Iparraguirre, Leire Alberro, Ainhoa Iñiguez, Saioa GS Muñoz-Culla, Maider Vergara, Itziar Matheu, Ander Otaegui, David Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals |
title | Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals |
title_full | Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals |
title_fullStr | Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals |
title_full_unstemmed | Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals |
title_short | Blood RNA-Seq profiling reveals a set of circular RNAs differentially expressed in frail individuals |
title_sort | blood rna-seq profiling reveals a set of circular rnas differentially expressed in frail individuals |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10334614/ https://www.ncbi.nlm.nih.gov/pubmed/37434183 http://dx.doi.org/10.1186/s12979-023-00356-6 |
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