miR-378 associated with proliferation, migration and apoptosis properties in A549 cells and targeted NPNT in COPD

PeerJ

article

Guoqing Qian¹  Qi Liao⁴  Guoxiang Li²  Fengying Yin² 

[1] Department of Infectious Diseases, Ningbo Hospital of Zhejiang University, Zhejiang University;Department of Infectious Diseases, Ningbo First Hospital, Ningbo University;Division of Respiratory Medicine, National Institute for Health Research, Nottingham Biomedical Research Centre, University of Nottingham;Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathological and Physiological Technology, School of Medicine, Ningbo University

关键词: NPNT;    Nephronectin;    Emphysema;    COPD;    Chronic obstructive pulmonary disease;    microRNA;    miR-378;    microRNA-378;    Alveolar epithelium;    Alveolar epithelial cells;   

DOI  :  10.7717/peerj.14062

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

Background microRNAs contribute to the development and progression of chronic obstructive pulmonary disease (COPD). However, the underlying molecular mechanisms are largely unclear. The goal of this study was to investigate the roles of miR-378 in alveolar epithelial type II cells and identify molecular mechanisms which contribute to the pathogenesis of COPD. Materials and methods Human alveolar epithelial (A549) cells were cultured in Dulbecco’s Modified Eagle Medium. Cell proliferation was studied by using a cell counting kit-8 (CCK-8) and colony formation assays. Cell apoptosis and cell cycle were analyzed by flow cytometry and wound healing and Transwell were used to analyze the cell migration and. We performed bioinformatics analysis including target gene prediction, gene ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment and construction of protein-protein interaction (PPI) network. The expression of miR-378 and NPNT from publically available expression microarray of COPD lung tissues was analyzed. Results Overexpression of miR-378 significantly increases cell proliferation, migration, and suppress apoptosis. GO analysis demonstrated that the miR-378 involved in transcription, vascular endothelial growth factor receptor signaling pathway, phosphatidylinositol 3-kinase signaling, cell migration, blood coagulation, cell shape, protein stabilization and phosphorylation. Pathway enrichment showed that the 1,629 target genes of miR-378 were associated with mTOR, ErbB, TGF-β, MAPK, and FoxO signaling pathways. Notably, miR-378 directly targets Nephronectin in A549 cells, and miR-378 was upregulated while NPNT was downregulated in COPD lung tissue samples. Conclusions These findings suggest that miR-378 can regulate the proliferation, migration, and apoptosis of A549 cells and target NPNT. miR-378 increased in COPD lung tissues while NPNT decreased, and might prove a potential target for novel drug therapy.

【 授权许可】

CC BY