Qian Yan, Mao Zheng-Dao, Shi Yu-Jia, Liu Zhi-Guang, Cao Qi, Zhang Qian
Cell Physiol Biochem. 2018;50(3):1140-1153. doi: 10.1159/000494541. Epub 2018 Oct 24.
BACKGROUND/AIMS: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. This study aimed to identify overlapping or diverging dysregulated genes, lncRNAs, miRNAs and signaling pathways in smoking and non-smoking chronic obstructive pulmonary disease (COPD).
Compared to normal controls, we identified the shared and divergent differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in smoking and non-smoking COPD by RNA-sequencing and bioinformatics analysis. Functional annotation of DEmRNAs were performed. Both cis and trans-target DEmRNAs of DElncRNAs were identified. The target DEmRNAs of DEmiRNAs were identified as well. The DEmiRNA-DEmRNA-DElncRNA interaction network was constructed. QRT-PCR was performed to validat the selected DEmiRNAs, DEmRNA and DElncRNAs in COPD.
Compared to normal control, 1234 DEmRNAs, 96 DElncRNAs and 151 DEmiRNAs were identified in non-smoking patients with COPD; 670 DEmRNAs, 44 DElncRNAs and 63 DEmiRNAs were identified in smoking patients with COPD. Leukocyte transendothelial migration and pathways in cancer were significantly enriched pathways in non-smoking and smoking COPD, respectively. MiR-122-5p-A2M-LINC00987/A2M-AS1/ linc0061 interactions might play key roles in COPD irrespective with the smoking status. Let-7-ADRB1-HLA-DQB1-AS1 might play a key role in the pathogenesis of smoking COPD while miR-218-5p/miR15a-RORA-LOC101928100/LINC00861 and miR-218-5p/miR15a-TGFβ3-RORA-AS1 interactions might involve with non-smoking COPD.
We identified the shared and diverging genes, lncRNAs, miRNAs and their interactions and pathways in smoking and non-smoking COPD which provided clues for understanding the mechanism and developing novel diagnostic and therapeutic strategies for COPD.
背景/目的：慢性阻塞性肺疾病（COPD）是全球发病和死亡的主要原因。本研究旨在鉴定吸烟和非吸烟慢性阻塞性肺疾病（COPD）中重叠或不同的失调基因、长链非编码RNA（lncRNA）、微小RNA（miRNA）和信号通路。
通过RNA测序和生物信息学分析，与正常对照相比，我们鉴定了吸烟和非吸烟COPD中共享和不同的差异表达mRNA（DEmRNA）、miRNA（DEmiRNA）和lncRNA（DElncRNA）。对DEmRNA进行功能注释。鉴定了DElncRNA的顺式和反式靶向DEmRNA。也鉴定了DEmiRNA的靶向DEmRNA。构建了DEmiRNA-DEmRNA-DElncRNA相互作用网络。进行qRT-PCR以验证COPD中所选的DEmiRNA、DEmRNA和DElncRNA。
与正常对照相比，在非吸烟COPD患者中鉴定出1234个DEmRNA、96个DElncRNA和151个DEmiRNA；在吸烟COPD患者中鉴定出670个DEmRNA、44个DElncRNA和63个DEmiRNA。白细胞跨内皮迁移和癌症中的通路分别是非吸烟和吸烟COPD中显著富集的通路。无论吸烟状态如何，miR-122-5p-A2M-LINC00987/A2M-AS1/ linc0061相互作用可能在COPD中起关键作用。Let-7-ADRB1-HLA-DQB1-AS1可能在吸烟COPD的发病机制中起关键作用，而miR-218-5p/miR15a-RORA-LOC101928100/LINC00861和miR-218-5p/miR15a-TGFβ3-RORA-AS1相互作用可能与非吸烟COPD有关。
我们鉴定了吸烟和非吸烟COPD中共享和不同的基因、lncRNA、miRNA及其相互作用和通路，这为理解COPD的机制以及开发新的诊断和治疗策略提供了线索。
