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MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway
Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. This study aimed to examine whether miRNA expression abundance in total white blood cells (WBCs) facilitated the identification of ADHD and reflected its response to treatment. Furthermore, whether miR...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858317/ https://www.ncbi.nlm.nih.gov/pubmed/35184133 http://dx.doi.org/10.1038/s41398-022-01832-1 |
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author | Wang, Liang-Jen Kuo, Ho-Chang Lee, Sheng-Yu Huang, Lien-Hung Lin, Yuyu Lin, Pei-Hsien Li, Sung-Chou |
author_facet | Wang, Liang-Jen Kuo, Ho-Chang Lee, Sheng-Yu Huang, Lien-Hung Lin, Yuyu Lin, Pei-Hsien Li, Sung-Chou |
author_sort | Wang, Liang-Jen |
collection | PubMed |
description | Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. This study aimed to examine whether miRNA expression abundance in total white blood cells (WBCs) facilitated the identification of ADHD and reflected its response to treatment. Furthermore, whether miRNA markers facilitated the growth of the human cortical neuronal (HCN-2) cells was also investigated. Total WBC samples were collected from 145 patients and 83 controls, followed by RNA extraction and qPCR assays. Subsequently, WBC samples were also collected at the endpoint from ADHD patients who had undergone 12 months of methylphenidate treatment. The determined ΔCt values of 12 miRNAs were applied to develop an ADHD prediction model and to estimate the correlation with treatment response. The prediction model applying the ΔCt values of 12 examined miRNAs (using machine learning algorithm) demonstrated good validity in discriminating ADHD patients from controls (sensitivity: 96%; specificity: 94.2%). Among the 92 ADHD patients completing the 12-month follow-up, miR-140-3p, miR-27a-3p, miR-486-5p, and miR-151-5p showed differential trends of ΔCt values between treatment responders and non-responders. In addition, the in vitro cell model revealed that miR-140-3p and miR-126-5p promoted the differentiation of HCN-2 cells by enhancing the length of neurons and the number of junctions. Microarray and flow cytometry assays confirmed that this promotion was achieved by repressing apoptosis and/or necrosis. The findings of this study suggest that the expression levels of miRNAs have the potential to serve as both diagnostic and therapeutic biomarkers for ADHD. The possible biological mechanisms of these biomarker miRNAs in ADHD pathophysiology were also clarified. |
format | Online Article Text |
id | pubmed-8858317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88583172022-03-15 MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway Wang, Liang-Jen Kuo, Ho-Chang Lee, Sheng-Yu Huang, Lien-Hung Lin, Yuyu Lin, Pei-Hsien Li, Sung-Chou Transl Psychiatry Article Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder. This study aimed to examine whether miRNA expression abundance in total white blood cells (WBCs) facilitated the identification of ADHD and reflected its response to treatment. Furthermore, whether miRNA markers facilitated the growth of the human cortical neuronal (HCN-2) cells was also investigated. Total WBC samples were collected from 145 patients and 83 controls, followed by RNA extraction and qPCR assays. Subsequently, WBC samples were also collected at the endpoint from ADHD patients who had undergone 12 months of methylphenidate treatment. The determined ΔCt values of 12 miRNAs were applied to develop an ADHD prediction model and to estimate the correlation with treatment response. The prediction model applying the ΔCt values of 12 examined miRNAs (using machine learning algorithm) demonstrated good validity in discriminating ADHD patients from controls (sensitivity: 96%; specificity: 94.2%). Among the 92 ADHD patients completing the 12-month follow-up, miR-140-3p, miR-27a-3p, miR-486-5p, and miR-151-5p showed differential trends of ΔCt values between treatment responders and non-responders. In addition, the in vitro cell model revealed that miR-140-3p and miR-126-5p promoted the differentiation of HCN-2 cells by enhancing the length of neurons and the number of junctions. Microarray and flow cytometry assays confirmed that this promotion was achieved by repressing apoptosis and/or necrosis. The findings of this study suggest that the expression levels of miRNAs have the potential to serve as both diagnostic and therapeutic biomarkers for ADHD. The possible biological mechanisms of these biomarker miRNAs in ADHD pathophysiology were also clarified. Nature Publishing Group UK 2022-02-19 /pmc/articles/PMC8858317/ /pubmed/35184133 http://dx.doi.org/10.1038/s41398-022-01832-1 Text en © The Author(s) 2022 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Liang-Jen Kuo, Ho-Chang Lee, Sheng-Yu Huang, Lien-Hung Lin, Yuyu Lin, Pei-Hsien Li, Sung-Chou MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway |
title | MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway |
title_full | MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway |
title_fullStr | MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway |
title_full_unstemmed | MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway |
title_short | MicroRNAs serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway |
title_sort | micrornas serve as prediction and treatment-response biomarkers of attention-deficit/hyperactivity disorder and promote the differentiation of neuronal cells by repressing the apoptosis pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8858317/ https://www.ncbi.nlm.nih.gov/pubmed/35184133 http://dx.doi.org/10.1038/s41398-022-01832-1 |
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