Liu Shaobo, He Qiang, Zhang NaNa, Li Yongbiao, Liu Qingshan
Key Laboratory of Ethnomedicine for Ministry of Education, Center On Translational Neuroscience, Minzu University of China, Beijing, 100000, China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Mol Neurobiol. 2025 May 5. doi: 10.1007/s12035-025-04949-8.
Stroke, a leading cause of death and adult disability, necessitates urgent advancements in prevention and treatment due to the lack of effective interventions. MicroRNAs (miRNAs), small noncoding RNAs, have emerged as crucial regulators in stroke pathology, influencing neuron cells through the blood-brain barrier. Our study integrated bioinformatics and experimental approaches to explore the potential of miRNAs as therapeutic targets and biomarkers for stroke. Analyzing RNA datasets, we identified 16 miRNAs and 382 mRNAs, with miR-3135b standing out as a key regulator. Utilizing bioinformatics tools, we predicted transcription factors and target genes, revealing the nuclear factor kappa B (NF-κB)/I-kappaB kinase beta (IKKβ) pathway's potential involvement. Experimental validation in a cerebral ischemia injury model demonstrated that intranasal administration of miR-3135b-agomir reversed protein levels of IKKβ and p65, inhibited the NF-κB pathway, and alleviated neuroinflammation. Behavioral assessments, molecular analyses, and immunofluorescence studies supported the therapeutic impact of miR-3135b, reducing infarct volume, enhancing neuronal regeneration, and mitigating inflammatory responses. Our findings underscore miR-3135b's promise as a therapeutic target in ischemic brain injury and advocate for further investigations into its relationship with neuroinflammation.
中风是导致死亡和成人残疾的主要原因，由于缺乏有效的干预措施，迫切需要在预防和治疗方面取得进展。微小RNA（miRNA）是一种小的非编码RNA，已成为中风病理过程中的关键调节因子，可通过血脑屏障影响神经元细胞。我们的研究综合了生物信息学和实验方法，以探索miRNA作为中风治疗靶点和生物标志物的潜力。通过分析RNA数据集，我们鉴定出16种miRNA和382种mRNA，其中miR-3135b是关键调节因子。利用生物信息学工具，我们预测了转录因子和靶基因，揭示了核因子κB（NF-κB）/I-κB激酶β（IKKβ）通路可能参与其中。在脑缺血损伤模型中的实验验证表明，经鼻给予miR-3135b-激动剂可逆转IKKβ和p65的蛋白水平，抑制NF-κB通路，并减轻神经炎症。行为评估、分子分析和免疫荧光研究支持了miR-3135b的治疗作用，可减少梗死体积，促进神经元再生，并减轻炎症反应。我们的研究结果强调了miR-3135b作为缺血性脑损伤治疗靶点的前景，并倡导进一步研究其与神经炎症的关系。
