LncRNA-LINC00472 contributes to the pathogenesis of atrial fibrillation (Af) by reducing expression of JP2 and RyR2 via miR-24

Abstract

Background: Dysregulated methylation of the promoter of lncRNA LINC00472 reduces the expression of LINC00472 and subsequently up-regulates the expression of its competing endogenous RNA miR-24. In addition, JP2 can stabilize the expression of RyR2, whereas the deregulation of RyR2 expression may contribute to the pathogenesis of atrial fibrillation (AF). In this study, we aimed to study the role of LINC00472 in the pathogenesis of AF. Methods: 125 AF patients and 168 healthy controls were enrolled to compare their expression of miR-24, LINC00472, JP2 and RyR2. A dual-luciferase reporter gene assay accompanied by real-time PCR, Western blot and IHC assay was subsequently conducted to evaluate the regulatory relationship among miR-24, LINC00472, JP2 and RyR2 in HCM and H9C2 cells. Results: AF patients were associated with an increased level of miR-24 expression and reduced level of LINC00472 expression. Also, the level of DNA methylation in LINC00472 was increased in AF patients. MiR-24 could negatively regulate the expression of LINC00472 and JP2 by directly binding to them. Conclusions: LINC00472 could regulate the progression of AF via modulating the LINC00472/miR-24/JP2/RyR2 signaling pathway.

Keywords

• Atrial fibrillation (AF)
• Methylation
• lncRNA-LINC00472
• miR-24
• JP2
• RyR2