Upregulated has-miR-4516 as a potential biomarker for early diagnosis of dust-induced pulmonary fibrosis in patients with pneumoconiosis.

Background: Pulmonary fibrosis (PF) is a representative pathological change in patients with pneumoconiosis; however, due to the absence of reliable and early biomarkers, microRNAs have recently emerged as potential candidates for identification. Objectives: The aim of our study was to discover the potential of PF-specific circulating microRNAs as early biomarkers among patients with pneumoconiosis. Methods: Four dust-exposed patients with PF and four matched healthy individuals (not exposed to dust) were recruited for the study. microRNA profiling was identified by micro-array and bioinformatics methods. Gene Ontology (GO) analysis was used to identify the potential biological or molecular processes modulated by these miRNAs. Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis was used to identify the potentially involved signaling pathways. miRNA-mRNA-binding network analysis was employed to identify genes potentially targeted by the miRNAs. Results: 1079 miRNAs were discovered, of which 406 were up-regulated and 117 were down-regulated in PF patients. 32 miRNAs were up-regulated by >4-fold and 17 miRNAs were down-regulated by >0.5 fold. GO analysis identified the biological processes affected by anatomical structure development, hemophilic cell adhesion and cell-cell adhesion via plasma membrane proteins. Target prediction software showed that serum has-miR-4516 targeted genes encoding basonuclin2, inhibitors of growth family member 4, the potassium voltage-gated channel, and "sha-1-related subfamily member 1" proteins. qRT-PCR revealed that has-miR-4516 was a potential biomarker of PF progression in patients with pneumoconiosis. Conclusions: Our findings suggest that the level of serum miR-4516 may be a potential biomarker for early diagnosis of PF in patients with pneumoconiosis. This is a pilot work that paves the way for a further functional study of the underlying regulatory mechanisms.