Abstract
Acute lung injury (ALI) is a life-threatening clinical condition associated with critically ill patients, and the construction of potential microRNA (miRNA) and messenger RNA (mRNA) regulatory networks will help to fully elucidate its underlying molecular mechanisms. First, we screened fifteen upregulated differentially expressed miRNAs (DE-miRNAs) and six downregulated DE-miRNAs from the Gene Expression Omnibus (GEO) database. Then, the predicted target genes of the upregulated and downregulated DE-miRNAs were identified from the miRNet database. Subsequently, differentially expressed mRNAs (DE-mRNAs) were identified from the GEO database and subjected to combined analysis with the predicted DE-miRNA target genes. Eleven target genes of the upregulated DE-miRNAs and one target gene of the downregulated DE-miRNAs were screened out. To further validate the prediction results, we randomly selected a dataset for subsequent analysis and found some accurate potential miRNA-mRNA regulatory axes, including mmu-mir-7b-5p-Gria1, mmu-mir-486a-5p-Shc4 and mmu-mir-486b-5p-Shc4 pairs. Finally, mir-7b and its target gene Gria1 and mir-486b and its target gene Shc4 were further validated in a bleomycin-induced ALI mouse model. We established a potential miRNA-mRNA regulatory network of ALI in mice, which may provide a basis for basic and clinical research on ALI and advance the available treatment options.
Highlights
Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are life-threatening clinical conditions associated with critically ill patients and have high morbidity and mortality rates worldwide[1]
The potential target genes for the upregulated DE-miRNAs included 1068 genes associated with 13 miRNAs, and the potential target genes for the downregulated DE-miRNAs included 76 genes associated with 4 miRNAs
ALI/ARDS is a life-threatening clinical condition associated with multiple symptoms and influenced by numerous factors[1,2]
Summary
Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) are life-threatening clinical conditions associated with critically ill patients and have high morbidity and mortality rates worldwide[1]. A range of microRNAs (miRNAs), recently determined by high-throughput screening studies in human and animal models, play a pivotal role in the pathophysiology of ALI/ARDS4,5. Circulatory miRNAs are beneficial biomarkers and some pharmacotherapeutic targets[8] This is revolutionary for syndromes that have neither measurable disease indicators nor targeted treatment. No miRNA and mRNA regulatory network of bleomycin-induced ALI in mice has been constructed. We searched datasets of bleomycin-induced ALI in mice by accessing the network database. We first screened differentially expressed miRNAs (DE-miRNAs) in bleomycin-treated lung tissues compared with normal lung tissues in mice. A potential miRNA-mRNA regulatory network was established, another dataset was used to detect the candidate target gene expression levels, and two relatively meaningful miRNA-mRNA pairs were experimentally verified.
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