Development of microRNA expression signature for emphysema in COPD patients. Homo sapiens

To define the role of microRNAs and their mRNA targets in emphysema severity in COPD patients. Overall design: We performed Agilent human miRNA oligo arrays (8x15K array, Part No. G4470A, Agilent Technologies) based on miRBase V9.1 on lung tissues from 9 mild and 20 moderate emphysema lungs obtained from patients undergoing curative resection for lung cancer. We identified 5 miRNAs and two of those were tested and validated technically using qRT-PCR. The predicted mRNA targets for the five miRNAs were identified in MSigDB using GSEA and their expression were negatively correlated in exvivo lung mRNA expression profile obtained from GEO datasets (GSE17770 and GSE1650). Increasing the expression of one of the miRNA target, miR-34c in BEAS-2B and HFL 1 cell lines resulted in the downregulation of 50 TargetScan and Pictar predicted targets of miR-34c.

本研究旨在阐明微小RNA（microRNAs）及其mRNA靶标在慢性阻塞性肺疾病（COPD）患者肺气肿严重程度中的作用。
实验设计：本研究基于miRBase V9.1数据库，对9例轻度肺气肿与20例中度肺气肿患者的肺癌根治术切除肺组织，采用安捷伦科技（Agilent Technologies）人类miRNA寡核苷酸芯片（8×15K芯片，部件号G4470A）完成检测。本研究共筛选得到5种微小RNA，其中2种通过实时定量聚合酶链反应（qRT-PCR）完成了技术验证。
本研究通过基因集富集分析（GSEA）在分子特征数据库（MSigDB）中筛选得到上述5种微小RNA的预测mRNA靶标；并从基因表达综合数据库（GEO）的数据集GSE17770与GSE1650中获取离体（ex vivo）肺组织mRNA表达谱，证实靶标基因的表达水平与对应微小RNA的表达水平呈负相关。在BEAS-2B与HFL 1细胞系中过表达miR-34c后，其50个经TargetScan与Pictar预测得到的靶标基因表达均出现下调。