Abstract
Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder caused by mutations in the SERPINA1 gene, and is characterized by lung emphysema and liver disease. AATD shows a high degree of phenotypic variability, which suggests that unknown genetic factors may influence disease severity. Since microRNAs (miRNAs) are involved in the pathogenesis of several human diseases, we investigated whether SERPINA1 gene could be regulated by these short single-stranded RNA molecules. In silico prediction revealed that miR-320c binds to the 3'UTR of SERPINA1 gene. We confirmed these results by luciferase reporter assay, and this mechanism was absent when a polymorphism was present in the target binding site of the gene. In addition, in vitro expression of miR-320c in HL60 cells led to downregulation of SERPINA1 gene. We further analyzed miR-320c expression in the blood of 35 patients with AATD and showed that this miRNA was overexpressed in patients with lung disease. Our results indicate that miR-320c regulates the expression of SERPINA1 gene, and its overexpression in blood could contribute to the pathogenesis of AATD.
- Copyright ©the authors 2016