Bakshi Gaganjyot Kaur, Khurana Sartaj, Srivastav Shambhavee, Kumar Rohit, Chourasia Mukesh, Bose Sudeep
Amity Institute of Biotechnology, Amity University Noida, Uttar Pradesh, India.
Department of Pulmonary and Critical Care Medicine, Safdarjung Hospital, Delhi, India.
Biotechnol Notes. 2025 Jan 28;6:79-88. doi: 10.1016/j.biotno.2025.01.003. eCollection 2025.
MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including sleep disorders. The aim of this study is to address the involvement of miRNAs (miR-21 and miR-29) in the pathophysiology of obstructive sleep apnea (OSA). In this study we have done integrated analysis of miRNAs with their potential gene targets as a strategy for management of OSA.
miRNA expression levels were quantified in healthy control group and obese vs. Non-obese OSA subjects by Quantitative real-time PCR. In-silico analysis of interplay of miRNAs with potential gene targets was done using Schrödinger Release 2023-1.
The real time expression analysis revealed a differential expression pattern in miRNAs indicating down-regulation of miR-21 in obese OSA while miR-29 showed upregulation as compared to non-obese OSA and healthy subjects with p values of ≤0.01 and <0.0001respectively. A trend was observed where target genes TGFBR2, NAMPT, and NPPB were significantly increased with p-value of ≤0.0001 and TGFBR3 and INSIG2 showed decreasing trend with p-value of ≤0.0001 between obese and non-obese OSA respectively. MD simulation analysis provided valuable information regarding the stability, flexibility, compactness and solvent exposure of the complexes over time.
miR-21 and miR-29 possesses differential expressions in obese OSA subject and exihbits strong molecular interactions with potential target genes, such as TGFBR2, NPPB, NAMPT and INSIG2. Identifying the miRNAs, genes and pathways associated with OSA can help to expand our understanding of the risk factors for the disease as well as provide new avenues for potential treatment.
微小RNA（miRNA）已被证明与包括睡眠障碍在内的人类疾病发病机制有关。本研究旨在探讨miRNA（miR-21和miR-29）在阻塞性睡眠呼吸暂停（OSA）病理生理学中的作用。在本研究中，我们对miRNA及其潜在基因靶点进行了综合分析，作为OSA管理的一种策略。
通过定量实时PCR对健康对照组以及肥胖与非肥胖OSA受试者的miRNA表达水平进行定量。使用Schrödinger Release 2023-1对miRNA与潜在基因靶点的相互作用进行计算机模拟分析。
实时表达分析显示miRNA存在差异表达模式，表明肥胖OSA患者中miR-21下调，而与非肥胖OSA患者和健康受试者相比，miR-29上调，p值分别≤0.01和<0.0001。观察到一种趋势，肥胖和非肥胖OSA患者之间，靶基因TGFBR2、NAMPT和NPPB显著增加，p值≤0.0001，而TGFBR3和INSIG2呈下降趋势，p值≤0.0001。分子动力学模拟分析提供了有关复合物随时间的稳定性、灵活性、紧凑性和溶剂暴露的有价值信息。
miR-21和miR-29在肥胖OSA患者中存在差异表达，并与潜在靶基因如TGFBR2、NPPB、NAMPT和INSIG2表现出强烈的分子相互作用。识别与OSA相关的miRNA、基因和途径有助于扩展我们对该疾病危险因素的理解，并为潜在治疗提供新途径。
