MicroRNA-708-3p as a potential therapeutic target via the ADAM17-GATA/STAT3 axis in idiopathic pulmonary fibrosis

MicroRNAs (miRNAs) are important diagnostic markers and therapeutic targets for many diseases. However, the miRNAs that control the pathogenesis of idiopathic pulmonary fibrosis (IPF) and act as potential therapeutic targets for the disease are rarely studied. In the present study, we analyzed the function and regulatory mechanism of microRNA-708-3p (miR-708-3p) and evaluated this marker’s potential as a therapeutic target in IPF. The clinical and biological relevance of fibrogenesis for miR-708-3p was assessed in vivo and in vitro, specifically in matching plasma and tissue samples from 78 patients with IPF. The data showed that the miR-708-3p levels decreased during fibrosis and inversely correlated with IPF. The experiments showed that the decreased miR-708 promoter activity and primer-miR-708(pri-miR-708) expression were the potential causes. By computational analysis, a dual luciferase reporter system, rescue experiments and a Cignal Finder 45-Pathway system with siADAM17 and a miR-708-3p mimic, we identified that miR-708-3p directly regulates its target gene, a disintegrin and metalloproteinase 17 (ADAM17), through a binding site in the 3′ untranslated region, which depends on the GATA/STAT3 signaling pathway. Finally, an miR-708-3p agomir was designed and used to test the therapeutic effects of the miR-708-3p in an animal model. Small-animal imaging technology and other experiments showed that the dynamic image distribution of the miR-708-3p agomir was mainly concentrated in the lungs and could block fibrogenesis. In conclusion, the miR-708-3p–ADAM17 axis aggravates IPF, and miR-708-3p can serve as a potential therapeutic target for IPF. Researchers have identified a molecule that may help to diagnose and treat idiopathic pulmonary fibrosis (IPF), a deadly lung disease. The lungs of patients with IPF develop extensive scarring, which makes breathing difficult and eventually leads to death. The causes are poorly understood, and few treatments are available, but researchers have begun to investigate miRNAs, small segments of RNA that regulate gene expression. Xiaodong Song, Changjun Lv and colleagues at Binzhou Medical University, Yantai City, China, investigated how miRNA-708-3p is involved in the progression of IPF. Using genetic analysis and mouse models, they showed that a decrease in miRNA-708-3p accelerated the progress of IPF. Analysis of samples from human patients confirmed this relationship. They conclude that miRNA-708-3p shows promise for diagnosis and treatment of IPF, and recommend further studies with larger numbers of patients.