Khurana Sartaj, Waidha Kamran, Guleria Randeep, Sharda Shivani, Bose Sudeep
Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India; Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh, India.
Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India.
Comput Biol Chem. 2020 Apr 18;87:107264. doi: 10.1016/j.compbiolchem.2020.107264.
Obstructive sleep apnoea (OSA) is a prevalent form of sleep disordered breathing which results in sleep fragmentation and deprivation. Obesity and cardiovascular disorders are the major risk factors associated with OSA. Molecular analysis of the factors associated with OSA could demarcate the clinical analysis pattern in a population.
This study pertains to in-silico analyses of miRNA and their gene targets with validation for their potential role in OSA as putative biomarker candidates.
miRDB, TargetScan and miRanda databases were used to identify targets of miR-27 and let-7 that have documented role in OSA and co-related obesity and cardiovascular disorders. Quantitative PCR was used to analyze expression pattern of miR-27 and let-7 in obese and non-obese OSA patient cohorts with respective controls. In-silico analysis was done using PatchDoc to obtain atomic contact energy (ACE) scores that indicated the docked gene targets to the predicted miRNA structures. The docked structures were analysed using Maestro Suite 11 for the hydrogen and aromatic interactions.
Downregulation of miR-27 and let-7 in OSA compared to controls was observed. In-silico data analysis was performed for gene targets (TGFBR1, TGFBR2, SMAD2, SMAD4, CRY2 and CNR1) of the selected miRNAs (miR-27 and let-7). Among all, CNR1 and CRY2 were found to be better targets for miR-27 and let-7 respectively as per ACE scores, ROC scores and expression fold change in OSA.
Our study gives insights to the expression profiling of miR-27 and let-7 and explore a set of potential target genes (CNR1 and CRY2) of these two miRNAs for a promising clinical relevance in OSA.
阻塞性睡眠呼吸暂停（OSA）是睡眠呼吸障碍的一种常见形式，会导致睡眠片段化和剥夺。肥胖和心血管疾病是与OSA相关的主要危险因素。对与OSA相关因素的分子分析可以划定人群中的临床分析模式。
本研究涉及对miRNA及其基因靶点的计算机分析，并验证它们在OSA中作为假定生物标志物候选物的潜在作用。
使用miRDB、TargetScan和miRanda数据库来识别在OSA以及相关的肥胖和心血管疾病中起作用的miR-27和let-7的靶点。采用定量PCR分析肥胖和非肥胖OSA患者队列及其各自对照中miR-27和let-7的表达模式。使用PatchDoc进行计算机分析以获得原子接触能量（ACE）分数，该分数表明对接的基因靶点与预测的miRNA结构。使用Maestro Suite 11分析对接结构的氢和芳香族相互作用。
与对照组相比，观察到OSA中miR-27和let-7的表达下调。对所选miRNA（miR-27和let-7）的基因靶点（TGFBR1、TGFBR2、SMAD2、SMAD4、CRY2和CNR1）进行了计算机数据分析。根据ACE分数、ROC分数和OSA中的表达倍数变化，发现CNR1和CRY2分别是miR-27和let-7的更好靶点。
我们的研究深入了解了miR-27和let-7的表达谱，并探索了这两种miRNA的一组潜在靶基因（CNR1和CRY2）在OSA中的临床应用前景。
