Hou Jin, Zhao Lei, Yan Jing, Ren Xiaoyong, Zhu Kang, Gao Tianxi, Du Xiaoying, Luo Huanan, Li Zhihui, Xu Min
Department of Otorhinolaryngology, the Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China.
Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
J Int Med Res. 2019 Sep;47(9):4163-4182. doi: 10.1177/0300060519858900. Epub 2019 Jul 12.
To investigate the involvement of microRNAs (miRNAs) in the pathogenesis of obstructive sleep apnea-hypopnea syndrome (OSAHS).
In this study, we investigated miRNA profiles in the upper airway (UA) skeletal muscles of four patients with OSAHS and four matched controls using the miRCURY miRNA array. In another cohort of 12 OSAHS cases and 7 controls, the mRNA expression levels of interleukin (IL)-6 and Lin-28 homolog A (Lin28A), targets of the downregulated let-7 family members, were measured by real-time quantitative-PCR. The potential targets of the miRNAs were predicted by miRNA target prediction databases miRanda, Microcosm, and Targetscan.
The array identified 370 differentially expressed miRNAs, of which 181 were upregulated and 189 were downregulated in OSAHS patients (based on a fold-change >2.0 and < 0.05). Upregulation of IL-6 and Lin28A was validated by quantitative reverse transcription PCR. The 612 targets predicted by all three algorithms were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The results revealed perturbations in signaling pathways and cellular functions.
This study demonstrated profoundly altered miRNA expression profiles in upper airway muscular tissues of patients with OSAHS, which might contribute to the formation and development of OSAHS.
探讨微小RNA(miRNA)在阻塞性睡眠呼吸暂停低通气综合征(OSAHS)发病机制中的作用。
在本研究中,我们使用miRCURY miRNA芯片研究了4例OSAHS患者和4例匹配对照的上气道(UA)骨骼肌中的miRNA谱。在另一组由12例OSAHS病例和7例对照组成的队列中,通过实时定量PCR测量白细胞介素(IL)-6和Lin-28同源物A(Lin28A)(下调的let-7家族成员的靶标)的mRNA表达水平。通过miRNA靶标预测数据库miRanda、Microcosm和Targetscan预测miRNA的潜在靶标。
芯片鉴定出370个差异表达的miRNA,其中181个在OSAHS患者中上调,189个下调(基于变化倍数>2.0且<0.05)。通过定量逆转录PCR验证了IL-6和Lin28A的上调。对所有三种算法预测的612个靶标进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路分析。结果揭示了信号通路和细胞功能的紊乱。
本研究表明OSAHS患者上气道肌肉组织中miRNA表达谱发生了深刻改变,这可能有助于OSAHS的形成和发展。