Identification and Bioinformatic Analysis of Circular RNA Expression in Peripheral Blood Mononuclear Cells from Patients with Chronic Obstructive Pulmonary Disease
单位:[1]Peking University China-Japan FriendshipSchool of Clinical Medicine, Beijing,People’s Republic of China[2]Departmentof Pulmonary and Critical Care Medicine,China-Japan Friendship Hospital, Beijing,People’s Republic of China[3]NationalClinical Research Center for RespiratoryDiseases, Beijing, People’s Republic ofChina[4]Institute of Respiratory Medicine,Chinese Academy of Medical Sciences,Beijing, People’s Republic of China[5]Institute of Clinical Medical Sciences,China-Japan Friendship Hospital, Beijing,People’s Republic of China[6]ChineseAcademy of Medical Sciences & PekingUnion Medical College, Beijing, People’sRepublic of China[7]Department ofGenetics and Genomic Sciences, IcahnSchool of Medicine at Mount Sinai, NewYork, NY, USA
Purpose: Circular RNAs (circRNAs) regulate other RNA transcripts by competing for shared microRNAs, which play roles in the pathogenesis of many diseases, including chronic obstructive pulmonary disease (COPD). However, the role of circRNAs in COPD remains unknown. This study aimed to investigate the expression profile and the role of circRNAs in COPD. Patients and Methods: Twenty-one COPD patients and twenty-one normal controls were recruited. Total RNAs were collected from peripheral blood mononuclear cells (PBMCs) of each participant. CircRNAs and protein-coding mRNAs were profiled by microarray and systematically compared between patients with COPD and control subjects. The top differentially expressed circRNAs and mRNAs were validated by quantitative real-time PCR (RTqPCR). Functional analysis identified pathways relevant to the pathogenesis of COPD. Next, the circRNA target pathway network, the circRNA-miRNA-mRNA network (ceRNA network) and functional ceRNA regulatory modules were constructed. Results: In total, 2132 circRNAs and 2734 protein-coding mRNAs were differentially expressed (vertical bar fold change vertical bar >1.5 and P-value <0.05) in COPD patients. Six out of nine selected RNAs were confirmed by RT-qPCR validation. Our functional analysis suggested that immune imbalances and inflammatory responses play roles in the pathogenesis of COPD. The ceRNA network highlighted the differentially expressed circRNAs and their related miRNAs and mRNAs in COPD. In the circRNA target pathway network and functional ceRNA regulatory modules, hsa_circRNA_0008672 appeared in the top three KEGG pathways (NOD-like receptor signaling pathway, natural killer cell mediated cytotoxicity and Th17 cell differentiation) and may act as the miRNA sponge regulating the hsa_circRNA_0008672/miR-1265/MAPK1 axis. Conclusion: Our findings demonstrate critical roles of the circRNAs in COPD molecular etiology. The data support a plausible mechanism that circRNAs may be involved in the development of COPD by affecting the immune balance. Moreover, the hsa_circRNA_0008672/miR1265/MAPK1 axis may contribute to the pathogenesis of COPD, warranting further investigation.
基金:
National Key R&D Program of China [2016YFC0206502, 2016YFC1303900]; National Nature Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81970043, 91643115, 91643201]; National Research Program for Key Issues in Air Pollution Control of China [DQGG0402]; CAMS Innovation Fund for Medical Sciences (CIFMS) [2018-I2M-1-001]
第一作者单位:[1]Peking University China-Japan FriendshipSchool of Clinical Medicine, Beijing,People’s Republic of China[2]Departmentof Pulmonary and Critical Care Medicine,China-Japan Friendship Hospital, Beijing,People’s Republic of China[3]NationalClinical Research Center for RespiratoryDiseases, Beijing, People’s Republic ofChina[4]Institute of Respiratory Medicine,Chinese Academy of Medical Sciences,Beijing, People’s Republic of China
通讯作者:
通讯机构:[1]Peking University China-Japan FriendshipSchool of Clinical Medicine, Beijing,People’s Republic of China[2]Departmentof Pulmonary and Critical Care Medicine,China-Japan Friendship Hospital, Beijing,People’s Republic of China[3]NationalClinical Research Center for RespiratoryDiseases, Beijing, People’s Republic ofChina[4]Institute of Respiratory Medicine,Chinese Academy of Medical Sciences,Beijing, People’s Republic of China[6]ChineseAcademy of Medical Sciences & PekingUnion Medical College, Beijing, People’sRepublic of China[*1]Peking University China-Japan Friendship School of Clinical Medicine, No. 2, East Yinghua Road, Chaoyang District, Beijing 100029, People’s Republic of China
推荐引用方式(GB/T 7714):
Duan Ruirui,Niu Hongtao,Yu Tao,et al.Identification and Bioinformatic Analysis of Circular RNA Expression in Peripheral Blood Mononuclear Cells from Patients with Chronic Obstructive Pulmonary Disease[J].INTERNATIONAL JOURNAL of CHRONIC OBSTRUCTIVE PULMONARY DISEASE.2020,15:1391-1401.doi:10.2147/COPD.S252896.
APA:
Duan, Ruirui,Niu, Hongtao,Yu, Tao,Cui, Han,Yang, Ting...&Wang, Chen.(2020).Identification and Bioinformatic Analysis of Circular RNA Expression in Peripheral Blood Mononuclear Cells from Patients with Chronic Obstructive Pulmonary Disease.INTERNATIONAL JOURNAL of CHRONIC OBSTRUCTIVE PULMONARY DISEASE,15,
MLA:
Duan, Ruirui,et al."Identification and Bioinformatic Analysis of Circular RNA Expression in Peripheral Blood Mononuclear Cells from Patients with Chronic Obstructive Pulmonary Disease".INTERNATIONAL JOURNAL of CHRONIC OBSTRUCTIVE PULMONARY DISEASE 15.(2020):1391-1401