Pang Xiaomin, Xiao Fang, Zheng Tianqing, Zhao Liren, Ge Xiaorong, Xie Shaojun, Zhang Zhao, Xu Ning, Wei Zongyong, Xiao Zhanhong
Department of Rehabilitation, the First People's Hospital of Nanning, the Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
Department of Neurology, the First Peoples Hospital of Nanning, the Fifth Affiliated Hospital of Guangxi Medical University, Nanning, China.
Biochem Genet. 2024 Sep 21. doi: 10.1007/s10528-024-10912-4.
The aim of this study was to explore the molecular mechanisms underlying cerebellar transcranial direct current stimulation (ctDCS) as a rehabilitation intervention for patients with ischemic stroke, focusing on the role of microRNAs (miRNAs). Whole-transcriptome sequencing was employed to obtain circulating expression profiles of miRNAs, long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and mRNAs in patients with ischemic stroke before and after 3-week ctDCS. miRanda software was used to predict the target genes of miRNAs, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to identify biological functions and signaling pathways. Subsequently, competing endogenous RNA (ceRNA) regulatory networks comprising circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA interactions were constructed. Key miRNAs in blood samples were validated through quantitative RT-PCR. In total, 43 miRNAs, 807 lncRNAs, 1,111 circRNAs, and 201 mRNAs were differentially expressed after ctDCS compared with before ctDCS. Bioinformatics analyses revealed significant enrichment of target genes regulated by differentially expressed miRNAs across multiple biological pathways. CeRNA regulatory networks implied that several miRNAs were closely related to the ctDCS. Among them, hsa-miR-181a-5p, hsa-miR-224-5p, and hsa-miR-340-3p showed significantly downregulated expression levels as confirmed by qRT-PCR. This study conducted the first-ever assessment of miRNA expression patterns in patients with ischemic stroke undergoing ctDCS. The findings revealed that ctDCS induces alterations in miRNA levels, suggesting their potential utility as therapeutic markers.
本研究旨在探讨小脑经颅直流电刺激（ctDCS）作为缺血性中风患者康复干预手段的分子机制，重点关注微小RNA（miRNA）的作用。采用全转录组测序获取缺血性中风患者在3周ctDCS治疗前后miRNA、长链非编码RNA（lncRNA）、环状RNA（circRNA）和mRNA的循环表达谱。使用miRanda软件预测miRNA的靶基因，同时进行基因本体（GO）和京都基因与基因组百科全书（KEGG）分析以确定生物学功能和信号通路。随后，构建了包含circRNA-miRNA-mRNA和lncRNA-miRNA-mRNA相互作用的竞争性内源性RNA（ceRNA）调控网络。通过定量RT-PCR验证血样中的关键miRNA。与ctDCS治疗前相比，ctDCS治疗后共有43种miRNA、807种lncRNA、1111种circRNA和201种mRNA差异表达。生物信息学分析显示，差异表达miRNA调控的靶基因在多个生物学途径中显著富集。ceRNA调控网络表明，几种miRNA与ctDCS密切相关。其中，经qRT-PCR证实，hsa-miR-181a-5p、hsa-miR-224-5p和hsa-miR-340-3p的表达水平显著下调。本研究首次评估了接受ctDCS治疗的缺血性中风患者的miRNA表达模式。研究结果表明，ctDCS可诱导miRNA水平的改变，提示其作为治疗标志物的潜在用途。
