Integrated analysis of transcription factor, microRNA and LncRNA in an animal model of obliterative bronchiolitis.
Obliterative bronchiolitis (OB) is characterized by sub-epithelial inflammatory and fibrotic narrowing of the bronchioles, and it is the predominant factor limiting long-term survival after lung transplantation. To explore molecular mechanism of OB, we investigated the interaction of transcription factor (TF), microRNA, long noncoding RNA (lncRNA), and gene expression in the mice model of OB by integrated analysis of TF array, miRNA microarray, and lncRNA and mRNA microarray. After 28 days of orthotopic tracheal transplantation in mice, 42 TFs were significantly up-regulated in allogeneic graft compared to syngeneic graft; 62 miRNAs including miR-376-5p were up-regulated and 17 miRNAs including miR-338-3p were down-regulated over 2-fold; 137 mRNAs were down-regulated and 129 mRNAs were up-regulated over 2-fold; 234 lncRNAs were up-regulated and 212 lncRNAs were down-regulated over 2-fold in the allogeneic model compared to that in the syngeneic control group. We further analyzed potential interaction between TFs, miRNAs, lncRNAs and target genes by different algorithms. Four differentially expressed TFs (Myc/Max, FOXO1, FOXM1, and SMAD) were predicted to regulate 3 different miRNAs, 17 mRNAs, and 16 lncRNAs. These findings suggest that modulation of altered transcription factors such as Myc/Max and FOXO1, and miRNAs such as miR-376-5p and miR-338-3p may become a preventive or therapeutic targets in the chronic lung allograft dysfunction.
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital China.
Ming
M
Dong
Department of Pediatric Surgery, Tianjin Children's Hospital China.
Xin
X
Wang
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital China.
Hong-Lin
HL
Zhao
Basic Medical College, Tianjin Medical University China.
Xing-Long
XL
Chen
Basic Medical College, Tianjin Medical University China.
Jing-Hua
JH
Yuan
School of Food Engineering and Biological Technology, Tianjin University of Science & Technology China.
Jiu-Yi
JY
Guo
Basic Medical College, Tianjin Medical University China.
Ke-Qiu
KQ
Li
Basic Medical College, Tianjin Medical University China.
Guang
G
Li
D000818:Animals; D001989:Bronchiolitis Obliterans / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic; D004195:Disease Models, Animal; D005260:Female; D000072278:Forkhead Box Protein M1; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014132:Trachea / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D000072278:Forkhead Box Protein M1; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse; C467200:Foxo1 protein, mouse; C000594936:MIRN376 microRNA, mouse; D035683:MicroRNAs; C000591274:Mirn338 microRNA, mouse; C489428:Myc protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; D051785:Smad Proteins; D014157:Transcription Factors
Obliterative bronchiolitis; molecular mechanism; orthotopic tracheal transplantation