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靶向心肌肌膜离子交换转录本的miR-454-3p和miR-194-5p是埃及儿童扩张型心肌病潜在的无创诊断生物标志物。

miR-454-3p and miR-194-5p targeting cardiac sarcolemma ion exchange transcripts are potential noninvasive diagnostic biomarkers for childhood dilated cardiomyopathy in Egyptian patients.

作者信息

Fayez Alaaeldin G, Esmaiel Nora N, Salem Sohair M, Ashaat Engy A, El-Saiedi Sonia A, El Ruby Mona O

机构信息

Human Genetics and Genome Research Institute, National Research Centre, Dokki, Egypt.

Division of Pediatric Cardiology, Faculty of Medicine, Cairo University, Giza, Egypt.

出版信息

Egypt Heart J. 2022 Sep 8;74(1):65. doi: 10.1186/s43044-022-00300-x.

DOI:10.1186/s43044-022-00300-x
PMID:36076093
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9458794/
Abstract

BACKGROUND

Childhood dilated cardiomyopathy (CDCM) is the most common cardiomyopathy in children and it is risk factor to heart failure and sudden death. Most of the different etiologic factors which have been postulated to DCM are idiopathic, and its pathogenesis remains uncertain. So it was worth investigating the potential DCM pathogenicity models to establish early noninvasive diagnosis parameters especially in CDCM patients. Beside that miRNAs in the circulatory blood are genetically considered the best option for noninvasive diagnosis; also, implementation of miRNAs as early diagnostic markers for children with DCM is urgent because those children have high risk to sudden heart death. We aimed to identify discriminator diagnostic circulatory miRNA expression levels in CDCM patients.

RESULTS

The expression levels of miR-454-3p and miR-194-5p were found significant upregulated (p value = 0.001 and 0.018; CI 95%, respectively), while miR-875-3p was found significant downregulated (p value = 0.040; CI 95%). A receiver operating characteristic (ROC) curve analysis showed significant AUC = 1.000 and 0.798 for miR-454-3p and miR-194-5p, respectively, and the optimal discriminated diagnostic cut-points were computed by index of union (IU) method. Enrichment analysis for the potential targeted mature mRNAs by miR-454-3p and miR-194-5p pointed that Ca, Na and K ions homeostasis in cardiac sarcolemma consider potential CDCM pathogenicity model.

CONCLUSIONS

miR-454-3p and miR-194-5p are highly influencing noninvasive biomarkers for CDCM, and further circulatory miRNAs-implicated studies are highly recommended.

摘要

背景

儿童扩张型心肌病(CDCM)是儿童中最常见的心肌病,是心力衰竭和猝死的危险因素。大多数推测与扩张型心肌病相关的不同病因是特发性的,其发病机制仍不确定。因此,研究潜在的扩张型心肌病致病模型以建立早期无创诊断参数是值得的,尤其是在CDCM患者中。除此之外,循环血液中的微小RNA(miRNA)在遗传学上被认为是无创诊断的最佳选择;此外,将miRNA作为扩张型心肌病患儿的早期诊断标志物迫在眉睫,因为这些患儿有心脏猝死的高风险。我们旨在确定CDCM患者中有鉴别诊断意义的循环miRNA表达水平。

结果

发现miR-454-3p和miR-194-5p的表达水平显著上调(p值分别为0.001和0.018;95%置信区间),而miR-875-3p显著下调(p值=0.040;95%置信区间)。受试者工作特征(ROC)曲线分析显示,miR-454-3p和miR-194-5p的曲线下面积(AUC)分别为1.000和0.798,通过联合指数(IU)法计算出最佳鉴别诊断切点。对miR-454-3p和miR-194-5p潜在靶向的成熟mRNA进行的富集分析表明,心肌肌膜中的钙、钠和钾离子稳态被认为是潜在的CDCM致病模型。

结论

miR-454-3p和miR-194-5p是对CDCM有高度影响的无创生物标志物,强烈建议进一步开展与循环miRNA相关的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/98b4a6563101/43044_2022_300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/dde578b230d8/43044_2022_300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/50664bfbc6c7/43044_2022_300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/c54737327d1b/43044_2022_300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/98b4a6563101/43044_2022_300_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/dde578b230d8/43044_2022_300_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/50664bfbc6c7/43044_2022_300_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/c54737327d1b/43044_2022_300_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/38db/9458794/98b4a6563101/43044_2022_300_Fig4_HTML.jpg

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