The combination of decitabine with multi-omics confirms the regulatory pattern of the correlation between DNA methylation of the CACNA1C gene and atrial fibrillation.

Background: Studies have shown that DNA methylation of the CACNA1C gene is involved in the pathogenesis of various diseases and the mechanism of drug action. However, its relationship with atrial fibrillation (AF) remains largely unexplored. Objective: To investigate the association between DNA methylation of the CACNA1C gene and AF by combining decitabine (5-Aza-2'-deoxycytidine, AZA) treatment with multi-omics analysis. Methods: HepG2 cells were treated with AZA to observe the expression of the CACNA1C gene, which was further validated using gene expression microarrays. Pyrosequencing was employed to validate differentially methylated sites of the CACNA1C gene observed in DNA methylation microarrays. A custom DNA methylation dataset based on the MSigDB database was combined with ChIP-sequencing and RNA-sequencing data to explore the regulatory patterns of DNA methylation of the CACNA1C gene. Results: Treatment of HepG2 cells with three different concentrations of AZA (2.5 µM, 5.0 µM, and 10.0 µM) resulted in 1.6, 2.5, and 2.9-fold increases in the mRNA expression of the CACNA1C gene, respectively, compared to the DMSO group, with statistical significance at the highest concentration group ( Conclusion: The DNA methylation levels at three CpG sites in intron 30 of the CACNA1C gene are associated with AF status, and potentially regulated by ATF7IP and KAT2B.