Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease
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 pi...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1112 |
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| author | Chiara Vancheri Elena Morini Francesca Romana Prandi Francesco Barillà Francesco Romeo Giuseppe Novelli Francesca Amati |
| author_facet | Chiara Vancheri Elena Morini Francesca Romana Prandi Francesco Barillà Francesco Romeo Giuseppe Novelli Francesca Amati |
| author_sort | Chiara Vancheri |
| collection | DOAJ |
| description | 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, <i>p</i> ≤ 0.05). An integrated analysis of genome-wide DNA methylation and miRNA-seq results indicated a significant downregulation of hsa-miR-200c-3p (FC<sub>CAD</sub> = −2.97, <i>p</i> ≤ 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) (<i>p</i>-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 (FC<sub>CAD</sub> = −2; <i>p</i> = 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; <i>p</i> = 0.02) in distinguishing CAD from CTR. Moreover, we found a significant positive correlation between hsa-miR-200c-3p expression and creatinine clearance (R<sup>2</sup> = 0.212, <i>p</i> < 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) (<i>p</i> < 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. |
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| language | English |
| last_indexed | 2024-03-09T12:25:58Z |
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| spelling | doaj.art-9c189dc8331b4102bf4cc797583b89022023-11-30T22:35:34ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242111210.3390/ijms24021112Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery DiseaseChiara Vancheri0Elena Morini1Francesca Romana Prandi2Francesco Barillà3Francesco Romeo4Giuseppe Novelli5Francesca Amati6Unit of Medical Genetics, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, ItalyUnit of Medical Genetics, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, ItalyUnit of Cardiology, University Hospital “Tor Vergata”, 00133 Rome, ItalyUnit of Cardiology, University Hospital “Tor Vergata”, 00133 Rome, ItalyUnit of Cardiology, University Hospital “Tor Vergata”, 00133 Rome, ItalyUnit of Medical Genetics, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, ItalyUnit of Medical Genetics, Department of Biomedicine and Prevention, University of Rome “Tor Vergata”, 00133 Rome, ItalyCoronary 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, <i>p</i> ≤ 0.05). An integrated analysis of genome-wide DNA methylation and miRNA-seq results indicated a significant downregulation of hsa-miR-200c-3p (FC<sub>CAD</sub> = −2.97, <i>p</i> ≤ 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) (<i>p</i>-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 (FC<sub>CAD</sub> = −2; <i>p</i> = 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; <i>p</i> = 0.02) in distinguishing CAD from CTR. Moreover, we found a significant positive correlation between hsa-miR-200c-3p expression and creatinine clearance (R<sup>2</sup> = 0.212, <i>p</i> < 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) (<i>p</i> < 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.https://www.mdpi.com/1422-0067/24/2/1112hsa-miR-200c-3pgenomic biomarkercoronary artery diseasegenome-wide methylationmiRNA-sequencing |
| spellingShingle | Chiara Vancheri Elena Morini Francesca Romana Prandi Francesco Barillà Francesco Romeo Giuseppe Novelli Francesca Amati Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease International Journal of Molecular Sciences hsa-miR-200c-3p genomic biomarker coronary artery disease genome-wide methylation miRNA-sequencing |
| title | Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease |
| title_full | Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease |
| title_fullStr | Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease |
| title_full_unstemmed | Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease |
| title_short | Downregulation of Circulating Hsa-miR-200c-3p Correlates with Dyslipidemia in Patients with Stable Coronary Artery Disease |
| title_sort | downregulation of circulating hsa mir 200c 3p correlates with dyslipidemia in patients with stable coronary artery disease |
| topic | hsa-miR-200c-3p genomic biomarker coronary artery disease genome-wide methylation miRNA-sequencing |
| url | https://www.mdpi.com/1422-0067/24/2/1112 |
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