Wang Ruiying, Xu Jianying, Liu Hu, Zhao Zhiping
Department of Respiratory, Shanxi Dayi Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2017 Apr 6;12:1101-1112. doi: 10.2147/COPD.S130416. eCollection 2017.
COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors. The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue. Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found. For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls. Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction. Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients. For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated. Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D. Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups. In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD. The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment.
慢性阻塞性肺疾病（COPD）是一种由环境决定因素以及遗传风险因素引起的多因素疾病。COPD的患病率和死亡率持续上升，而COPD的诊断不足仍然是一个关键问题。先前的报告研究了有前景的微小RNA（miRNA）以揭示COPD发生发展的分子机制；然而，尚未找到COPD的诊断和治疗标志物。在本研究中，20名具有代表性的COPD患者根据病情严重程度增加分为四组（A、B、C和D组），并与6名健康对照进行比较。通过下一代测序分析外周血白细胞的小RNA谱，通过定量逆转录聚合酶链反应验证差异表达的miRNA。与健康对照相比，在COPD患者中发现了19种差异表达的miRNA。在所有COPD组中，miR-3177-3p下调，而17种miRNA上调。此外，结果显示有21种差异表达的miRNA，其中miR-183-5p从A组到B组再到D组持续下调。在COPD不同组（A、B、C和D组）各自的支气管扩张剂可逆性阳性和阴性组之间，有10种miRNA差异表达，而miR-100-5p在阴性组中上调。总之，miR-106b-5p、miR-125a-5p、miR-183-5p和miR-100-5p在COPD的发生发展中起关键作用。miR-106b-5p减轻了COPD的严重程度，因此表明该miRNA是疾病治疗的潜在靶点。
