MicroRNA-638 inhibits human aortic valve interstitial cell calcification by targeting Sp7

Calcific aortic valve disease (CAVD) is a complex heart valve disease involving a wide range of pathological changes. Emerging evidence indicates that osteogenic differentiation of human aortic valve interstitial cells (hAVICs) plays a key role in valve calcification. In this study, we aimed to investigate the function of miR-638 in hAVICs osteogenesis. Both miRNA microarray assay and qRT-PCR results demonstrating miR-638 was obviously up-regulated in calcific aortic valves compared with non-calcific valves. We also proved that miR-638 was significantly up-regulated during hAVICs osteogenic differentiation. Overexpression of miR-638 suppressed osteogenic differentiation of hAVICs in vitro, whereas down-regulation of miR-638 enhance the process. Target prediction analysis and dual-luciferase reporter assay confirmed that Sp7 transcription factor (Sp7) was a direct target of miR-638. Furthermore, knockdown of Sp7 inhibited osteogenic differentiation of hAVICs, which is similar to the results observed in up-regulation miR-638. Our data indicated that miR-638 plays an inhibitory role in hAVICs osteogenic differentiation, which may act by targeting Sp7. MiR-638 may be a potential therapeutic target for CAVD.