Coordination of PRKCA/PRKCA-AS1 interplay facilitates DNA methyltransferase 1 recruitment on DNA methylation to affect protein kinase C alpha transcription in mitral valve of rheumatic heart disease

Abstract

In the present study, mitral valve tissues from three mitral stenosis patients with RHD by valve replacement and two healthy donors were harvested and conducted DNA methylation signature on PRKCA by MeDIP-qPCR. The presence of hypomethylated CpG islands at promoter and 5ʹ terminal of PRKCA was observed in RHD accompanied with highly expressed PRKCA and downregulated antisense long non-coding RNA (lncRNA) PRKCA-AS1 compared to health control. Furthermore, the enrichments of DNMT1/3A/3B on PRKCA were detected by ChIP-qPCR assay in vivo and in human cardiomyocyte AC16 and RL-14 cells exposed to TNF-α in vitro, and both demonstrated that DNMT1 substantially contributed to DNA methylation. Additionally, PRKCA-AS1 was further determined to bind with promoter of PRKCA via 5ʹ terminal and interact with DNMT1 via 3ʹ terminal. Taken together, our results illuminated a novel regulatory mechanism of DNA methylation on regulating PRKCA transcription through lncRNA PRKCA-AS1, and shed light on the molecular pathogenesis of RHD occurrence.

NEAT1 variant 1 weakens the genome-wide effect of miR-3122 on blocking H3K79me3 in bladder cancer

“…The mechanism behind the opposite effects on tumor of NEAT1.1 and NEAT1.2 still remain obscure [13]. According to previous studies of the same kind non-coding RNAs in nucleus [14,15], lncRNA could facilitate the connection between transcription factors or epigenetic regulators and DNA elements. In our research, our data unexpectedly supports that a large number of nucleus-expressed RNAs are enriched on NEAT1.…”

The Role of Clonal Hematopoiesis of Indeterminant Potential and DNA (Cytosine-5)-Methyltransferase Dysregulation in Pulmonary Arterial Hypertension and Other Cardiovascular Diseases

“…Santos-Bezerra et al investigated the risk associated with DNMT1 mutations in diabetes and found that the DNMT1 SNP rs11085721 was associated with a risk of cardiovascular autonomic neuropathy in females with type I diabetes [140]. Lastly, downregulated lncRNA, protein kinase C alpha antisense RNA 1 (PRKCA-AS1) decreases DNMT1-mediated methylation (Figure 5) of the promoter region of protein kinase C alpha (PRKCA), and subsequently increases PRKCA expression in the mitral valves of patients with rheumatic heart disease, suggesting a DNMT-regulated mechanism in valvular heart disease [141].…”