Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease

Abstract

Coronary heart disease (CHD), one of the leading causes of disability and death worldwide, is a multifactorial disease whose early diagnosis is demanding. Thus, biomarkers predicting the occurrence of this pathology are of great importance from a clinical and therapeutic standpoint. By means of a pilot study on peripheral blood cells (PBMCs) of subjects with no coronary lesions (CTR; n = 2) and patients with stable CAD (CAD; n = 2), we revealed 61 differentially methylated regions (DMRs) (18 promoter regions, 24 genes and 19 CpG islands) and 14.997 differentially methylated single CpG sites (DMCs) in CAD patients. MiRNA-seq results displayed a peculiar miRNAs profile in CAD patients with 18 upregulated and 32 downregulated miRNAs (FC ≥ ±1.5, p ≤ 0.05). An integrated analysis of genome-wide DNA methylation and miRNA-seq results indicated a significant downregulation of hsa-miR-200c-3p (FCCAD = −2.97, p ≤ 0.05) associated to the hypermethylation of two sites (genomic coordinates: chr12:7073122-7073122 and chr12:7072599-7072599) located intragenic to the miR-200c/141 genomic locus (encoding hsa-miR-200c-3p) (p-value = 0.009) in CAD patients. We extended the hsa-miR-200c-3p expression study in a larger cohort (CAD = 72, CTR = 24), confirming its reduced expression level in CAD patients (FCCAD = −2; p = 0.02). However, when we analyzed the methylation status of the two CpG sites in the same cohort, we failed to identify significant differences. A ROC curve analysis showed good performance of hsa-miR-200c-3p expression level (AUC = 0.65; p = 0.02) in distinguishing CAD from CTR. Moreover, we found a significant positive correlation between hsa-miR-200c-3p expression and creatinine clearance (R2 = 0.212, p < 0.005, Pearson r = 0.461) in CAD patients. Finally, a phenotypic correlation performed in the CAD group revealed lower hsa-miR-200c-3p expression levels in CAD patients affected by dyslipidemia (+DLP, n = 58) (p < 0.01). These results indicate hsa-miR-200c-3p as potential epi-biomarker for the diagnosis and clinical progression of CAD and highlight the importance of deeper studies on the expression of this miRNA to understand its functional role in coronary artery disease development.

Role of miR-128-3p and miR-195-5p as biomarkers of coronary artery disease In Indians: A Pilot study

“…Several micro RNAs have been reported over the years which regulate coronary artery disease [23][24][25][26][27][28] . Some of these micro RNAs are present in circulation and few have been reported to be differentially expressed in serum/plasma [26][27][28][29] .…”

“…Several micro RNAs have been reported over the years which regulate coronary artery disease [23][24][25][26][27][28] . Some of these micro RNAs are present in circulation and few have been reported to be differentially expressed in serum/plasma [26][27][28][29] . To report a few, Ling H et al (2020) found that the exosomal miR-126 levels were positively correlated in cases of unstable angina (n = 31) as well as acute myocardial infarction (n = 34) 30 .…”

An RNA-seq study in Friedreich ataxia patients identified hsa-miR-148a-3p as a putative prognostic biomarker of the disease

“…Among the best-studied epigenetic mechanisms, microRNAs (miRNAs) are a group of small non-coding RNA molecules ( ∼ 22 nucleotides in length) that regulate gene expression at post-transcriptional level by binding specific mRNA targets. Many studies have demonstrated that miRNAs are critically involved in important biological processes in healthy and diseased conditions, including cancer, Alzheimer's disease, cardiovascular diseases, viral infections and diabetes [24][25][26][27][28][29]. Dysregulated expression of specific miRNAs can contribute to disease progression by affecting critical signaling pathways and gene networks.…”