中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
Chinese Journal of Medical Genetics
2015年
5期
641-646
,共6页
范惠民%牛威%何明骏%孔令明%仲爱芳%张巧丽%闫妍%张理义
範惠民%牛威%何明駿%孔令明%仲愛芳%張巧麗%閆妍%張理義
범혜민%우위%하명준%공령명%중애방%장교려%염연%장리의
miRNA%焦虑症%靶基因%生物信息学
miRNA%焦慮癥%靶基因%生物信息學
miRNA%초필증%파기인%생물신식학
miRNA%Anxiety disorder%Target gene prediction%Bioinformatics
目的 对在焦虑症患者外周血单核细胞中差异性表达的microRNA(miRNA)进行生物信息学分析,以探讨外周血microRNA在焦虑症发病中的作用.方法 采用miRNA芯片对焦虑症患者外周血单核细胞中的miRNA进行筛查,应用实时定量PCR技术对差异性表达的miRNA进行验证,最后对目标miRNA进行生物信息学分析.结果 芯片筛查结果提示有7个成熟miRNA在焦虑症患者中出现差异性表达,实时定量PCR验证实验提示其中5个miRNA(has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p以及has-miR-663)在病例组中显著上调.上述5个miRNA的靶基因的合集为195个.后者参与神经系统的发育与调节过程、转录过程调节、多种器官发育、生物种间相互作用、细胞分化、RNA转运、神经系统发育、细胞间信号转导、神经元发育等(P＜0.05),所涉及的KEGG信号通路包括谷氨酸能突触、轴突导向、趋化因子信号通路、钙离子信号通路、MAPK信号通路、GnRH信号通路、Wnt信号通路、间隙连接、长时程增强、VEGF信号通路、凋亡、以及B细胞受体信号通路等(P＜0.05).miRNA-GO生物学过程网络图及miRNA-KEGG pathway网络图提示,has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p在焦虑症中可能起着更为重要的作用.结论 焦虑症患者外周血单核细胞中has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p以及has-miR-663出现差异性表达,生物信息学分析提示上述5个miRNA与焦虑症的发病机制密切相关.
目的 對在焦慮癥患者外週血單覈細胞中差異性錶達的microRNA(miRNA)進行生物信息學分析,以探討外週血microRNA在焦慮癥髮病中的作用.方法 採用miRNA芯片對焦慮癥患者外週血單覈細胞中的miRNA進行篩查,應用實時定量PCR技術對差異性錶達的miRNA進行驗證,最後對目標miRNA進行生物信息學分析.結果 芯片篩查結果提示有7箇成熟miRNA在焦慮癥患者中齣現差異性錶達,實時定量PCR驗證實驗提示其中5箇miRNA(has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p以及has-miR-663)在病例組中顯著上調.上述5箇miRNA的靶基因的閤集為195箇.後者參與神經繫統的髮育與調節過程、轉錄過程調節、多種器官髮育、生物種間相互作用、細胞分化、RNA轉運、神經繫統髮育、細胞間信號轉導、神經元髮育等(P＜0.05),所涉及的KEGG信號通路包括穀氨痠能突觸、軸突導嚮、趨化因子信號通路、鈣離子信號通路、MAPK信號通路、GnRH信號通路、Wnt信號通路、間隙連接、長時程增彊、VEGF信號通路、凋亡、以及B細胞受體信號通路等(P＜0.05).miRNA-GO生物學過程網絡圖及miRNA-KEGG pathway網絡圖提示,has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p在焦慮癥中可能起著更為重要的作用.結論 焦慮癥患者外週血單覈細胞中has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p以及has-miR-663齣現差異性錶達,生物信息學分析提示上述5箇miRNA與焦慮癥的髮病機製密切相關.
목적 대재초필증환자외주혈단핵세포중차이성표체적microRNA(miRNA)진행생물신식학분석,이탐토외주혈microRNA재초필증발병중적작용.방법 채용miRNA심편대초필증환자외주혈단핵세포중적miRNA진행사사,응용실시정량PCR기술대차이성표체적miRNA진행험증,최후대목표miRNA진행생물신식학분석.결과 심편사사결과제시유7개성숙miRNA재초필증환자중출현차이성표체,실시정량PCR험증실험제시기중5개miRNA(has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p이급has-miR-663)재병례조중현저상조.상술5개miRNA적파기인적합집위195개.후자삼여신경계통적발육여조절과정、전록과정조절、다충기관발육、생물충간상호작용、세포분화、RNA전운、신경계통발육、세포간신호전도、신경원발육등(P＜0.05),소섭급적KEGG신호통로포괄곡안산능돌촉、축돌도향、추화인자신호통로、개리자신호통로、MAPK신호통로、GnRH신호통로、Wnt신호통로、간극련접、장시정증강、VEGF신호통로、조망、이급B세포수체신호통로등(P＜0.05).miRNA-GO생물학과정망락도급miRNA-KEGG pathway망락도제시,has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p재초필증중가능기착경위중요적작용.결론 초필증환자외주혈단핵세포중has-miR-4484、has-miR-4505、has-miR-4674、has-miR-501-3p이급has-miR-663출현차이성표체,생물신식학분석제시상술5개miRNA여초필증적발병궤제밀절상관.
Objective To identify differentially expressed microRNAs(miRNA) in peripheral blood mononuclear cells(PBMCs) of anxiety patients and predict their target genes and function by bioinformatics analysis.Methods The miRNA expression profiles were determined using an Affymetrix array.To validate the results, real-time quantitative polymerase chain reaction(qRT-PCR) analysis in a larger cohort was employed.The targets of the differentially expressed miRNAs were predicted by Target Scan, miRBD, and DIANA-microT-CDS, and the results were analyzed by gene ontology(GO) and KEGG pathway analysis using FunNet.Results MicroRNA microarray chip analysis has identified 7 miRNAs were detected with significant changes in expression in PBMCs of anxiety patients.qRT-PCR analysis has confirmed that the expression levels of 5 miRNAs(has-miR-4484, has-miR-4505, has-miR-4674, has-miR-501-3p and has-miR-663) were up-regulated.Intersecting the genes by Target Scan, miRBD, and DIANA-microT-CDS has predicted 195 targets.GO analysis showed that biological processes regulated by the predicted target genes have included diverse terms.Some terms, e.g., nervous system development, nerve growth factor receptor signaling pathway, neuron migration, dendrite development, regulation of neuron projection development,midbrain development , regulation of excitatory postsynaptic membrane potential, gliogenesis, dendrite morphogenesis, etc.have direct relationship with the central nervous system and brain functions.Pathway analysis showed that a significant enrichment in several pathways related to neuronal brain functions such as glutamatergic synapse, axon guidance, calcium signaling pathway, MAPK signaling pathway, GnRH signaling pathway, Wnt signaling pathway, gap junction, long-term potentiation and VEGF signaling pathway, etc.Among the five microRNAs, has-miR-4484, has-miR-4505, has-miR-4674 and has-miR-501-3p may have more important regulatory functions.Conclusion Five miRNAs (has-miR-4484, has-miR-4505, has-miR-4674, has-miR-501-3p and has-miR-663) are up-regulated in PBMCs of anxiety patients and may be closely involved in the pathogenesis of anxiety disorder.
