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

作者全名："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"

作者地址："[Wang, Haiyang; Zhang, Hongmei; Song, Jinlin; Ji, Ping; Xie, Peng] Stomatol Hosp Chongqing Med Univ, Key Lab Psychoseomadsy, Chongqing, Peoples R China; [Wang, Haiyang; Zhang, Hongmei; Song, Jinlin; Ji, Ping; Xie, Peng] Affiliated Stomatol Hosp Chongqing Med Univ, Collegeof Stomatol, Chongqing, Peoples R China; [Wang, Haiyang; Zhang, Hongmei; Song, Jinlin; Ji, Ping; Xie, Peng] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Wang, Haiyang; Liu, Lanxiang; Chen, Xueyi; Zhou, Chanjuan; Rao, Xuechen; Li, Wenxia; Liu, Yiyun; Xie, Peng] First Affiliated Hosp Chongqing Med Univ, Natl Hlth Commiss Key Lab ofDiagnosis & Treatment, Chongqing, Peoples R China; [Liu, Lanxiang; Fang, Liang] Yongchuan Hosp Chongqing Med Univ, Dept Neurol, Chongqing, Peoples R China; [Chen, Xueyi; Li, Wenwen] Chongqing Med Univ, Fac Basic Med, Dept Pathol, Chongqing, Peoples R China"

通信作者："Ji, P; Xie, P (通讯作者)，Stomatol Hosp Chongqing Med Univ, Key Lab Psychoseomadsy, Chongqing, Peoples R China.; Ji, P; Xie, P (通讯作者)，Affiliated Stomatol Hosp Chongqing Med Univ, Collegeof Stomatol, Chongqing, Peoples R China.; Ji, P; Xie, P (通讯作者)，Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China.; Xie, P (通讯作者)，First Affiliated Hosp Chongqing Med Univ, Natl Hlth Commiss Key Lab ofDiagnosis & Treatment, Chongqing, Peoples R China."

来源：FRONTIERS IN PSYCHIATRY

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:000789592900001

JCR分区：Q2

影响因子：4.7

年份：2022

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：depression; miRNAs; mRNAs; Th17 cell differentiation; CSDS

摘要："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 IL1 beta, and the increased expression of retinoic acid receptor-related orphan receptor gamma-t (ROR gamma t) 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."

基金机构："National Key R&D Program of China [2017YFA0505700]; Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences [2019PT320002]; Natural Science Foundation Project of China [81820108015]; China Postdoctoral Science Foundation [2020TQ0393, 2020M683634XB, 2021M693926]"

基金资助正文："Funding This study was supported by the National Key R&D Program of China (Grant No. 2017YFA0505700), the Non-Profit Central Research Institute Fund of the Chinese Academy of Medical Sciences (Grant No. 2019PT320002), the Natural Science Foundation Project of China (Grant No. 81820108015), and the China Postdoctoral Science Foundation (Nos. 2020TQ0393, 2020M683634XB, and 2021M693926)."