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MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression

Accumulating evidence indicates an important role for microRNA (miRNA)–messenger RNA (mRNA) regulatory networks in human depression. However, the mechanisms by which these networks act are complex and remain poorly understood. We used data mining to identify differentially expressed miRNAs from GSE8...

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Autores principales: Wang, Haiyang, Liu, Lanxiang, Chen, Xueyi, Zhou, Chanjuan, Rao, Xuechen, Li, Wenxia, Li, Wenwen, Liu, Yiyun, Fang, Liang, Zhang, Hongmei, Song, Jinlin, Ji, Ping, Xie, Peng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017773/
https://www.ncbi.nlm.nih.gov/pubmed/35449567
http://dx.doi.org/10.3389/fpsyt.2022.824209
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author Wang, Haiyang
Liu, Lanxiang
Chen, Xueyi
Zhou, Chanjuan
Rao, Xuechen
Li, Wenxia
Li, Wenwen
Liu, Yiyun
Fang, Liang
Zhang, Hongmei
Song, Jinlin
Ji, Ping
Xie, Peng
author_facet Wang, Haiyang
Liu, Lanxiang
Chen, Xueyi
Zhou, Chanjuan
Rao, Xuechen
Li, Wenxia
Li, Wenwen
Liu, Yiyun
Fang, Liang
Zhang, Hongmei
Song, Jinlin
Ji, Ping
Xie, Peng
author_sort Wang, Haiyang
collection PubMed
description Accumulating evidence indicates an important role for microRNA (miRNA)–messenger RNA (mRNA) regulatory networks in human depression. However, the mechanisms by which these networks act are complex and remain poorly understood. We used data mining to identify differentially expressed miRNAs from GSE81152 and GSE152267 datasets, and differentially expressed mRNAs were identified from the Netherlands Study of Depression and Anxiety, the GlaxoSmithKline-High-Throughput Disease-specific target Identification Program, and the Janssen-Brain Resource Company study. We constructed a miRNA–mRNA regulatory network based on differentially expressed mRNAs that intersected with target genes of differentially expressed miRNAs, and then performed bioinformatics analysis of the network. The key candidate genes were assessed in the prefrontal cortex of chronic social defeat stress (CSDS) depression mice by quantitative real-time polymerase chain reaction (qRT-PCR). Three differentially expressed miRNAs were commonly identified across the two datasets, and 119 intersecting differentially expressed mRNAs were identified. A miRNA–mRNA regulatory network including these three key differentially expressed miRNAs and 119 intersecting differentially expressed mRNAs was constructed. Functional analysis of the intersecting differentially expressed mRNAs revealed that an abnormal inflammatory response characterized by disturbed T-helper cell 17 (Th17) differentiation was the primary altered biological function. qRT-PCR validated the decreased expression of Th17 cell differentiation-related genes, including interleukin (IL)17A, IL21, IL22, and IL1β, and the increased expression of retinoic acid receptor-related orphan receptor gamma-t (RORγt) in CSDS mice, which showed significant depressive- and anxiety-like behaviors. This study indicates that an abnormal inflammatory response characterized by disturbed Th17 cell differentiation is the primary altered biological process in major depressive disorder. Our findings indicate possible biomarkers and treatment targets and provide novel clues to understand the pathogenesis of major depressive disorder.
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spelling pubmed-90177732022-04-20 MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression Wang, Haiyang Liu, Lanxiang Chen, Xueyi Zhou, Chanjuan Rao, Xuechen Li, Wenxia Li, Wenwen Liu, Yiyun Fang, Liang Zhang, Hongmei Song, Jinlin Ji, Ping Xie, Peng Front Psychiatry Psychiatry Accumulating evidence indicates an important role for microRNA (miRNA)–messenger RNA (mRNA) regulatory networks in human depression. However, the mechanisms by which these networks act are complex and remain poorly understood. We used data mining to identify differentially expressed miRNAs from GSE81152 and GSE152267 datasets, and differentially expressed mRNAs were identified from the Netherlands Study of Depression and Anxiety, the GlaxoSmithKline-High-Throughput Disease-specific target Identification Program, and the Janssen-Brain Resource Company study. We constructed a miRNA–mRNA regulatory network based on differentially expressed mRNAs that intersected with target genes of differentially expressed miRNAs, and then performed bioinformatics analysis of the network. The key candidate genes were assessed in the prefrontal cortex of chronic social defeat stress (CSDS) depression mice by quantitative real-time polymerase chain reaction (qRT-PCR). Three differentially expressed miRNAs were commonly identified across the two datasets, and 119 intersecting differentially expressed mRNAs were identified. A miRNA–mRNA regulatory network including these three key differentially expressed miRNAs and 119 intersecting differentially expressed mRNAs was constructed. Functional analysis of the intersecting differentially expressed mRNAs revealed that an abnormal inflammatory response characterized by disturbed T-helper cell 17 (Th17) differentiation was the primary altered biological function. qRT-PCR validated the decreased expression of Th17 cell differentiation-related genes, including interleukin (IL)17A, IL21, IL22, and IL1β, and the increased expression of retinoic acid receptor-related orphan receptor gamma-t (RORγt) in CSDS mice, which showed significant depressive- and anxiety-like behaviors. This study indicates that an abnormal inflammatory response characterized by disturbed Th17 cell differentiation is the primary altered biological process in major depressive disorder. Our findings indicate possible biomarkers and treatment targets and provide novel clues to understand the pathogenesis of major depressive disorder. Frontiers Media S.A. 2022-04-05 /pmc/articles/PMC9017773/ /pubmed/35449567 http://dx.doi.org/10.3389/fpsyt.2022.824209 Text en Copyright © 2022 Wang, Liu, Chen, Zhou, Rao, Li, Li, Liu, Fang, Zhang, Song, Ji and Xie. 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 Psychiatry
Wang, Haiyang
Liu, Lanxiang
Chen, Xueyi
Zhou, Chanjuan
Rao, Xuechen
Li, Wenxia
Li, Wenwen
Liu, Yiyun
Fang, Liang
Zhang, Hongmei
Song, Jinlin
Ji, Ping
Xie, Peng
MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression
title MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression
title_full MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression
title_fullStr MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression
title_full_unstemmed MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression
title_short MicroRNA–Messenger RNA Regulatory Network Mediates Disrupted TH17 Cell Differentiation in Depression
title_sort microrna–messenger rna regulatory network mediates disrupted th17 cell differentiation in depression
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9017773/
https://www.ncbi.nlm.nih.gov/pubmed/35449567
http://dx.doi.org/10.3389/fpsyt.2022.824209
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