扩张型心肌病并发心力衰竭患者中参与花生四烯酸代谢调控的异常表达microRNAs的鉴定(英文)

Identification of dysregulated microRNAs involved in arachidonic acid metabolism regulation in dilated cardiomyopathy-mediated heart failure patients

心力衰竭作为一种具有较高发病率和死亡率的临床综合征,正成为日益严重的公共卫生问题。扩张型心肌病是心力衰竭的一种主要诱因,但其分子机制还有很多未知。之前的研究发现花生四烯酸(arachidonic acid,AA)代谢紊乱可导致心力衰竭的发生。为了探究调控花生四烯酸代谢的microRNAs(miRNAs)在扩张型心肌病并发心力衰竭过程中的作用,我们利用两个公共数据集中的miRNAs测序数据,分析了由扩张型心肌病引发的心力衰竭患者心肌组织中的miRNAs表达情况。我们分别在上述数据集中鉴定到101个和88个具有明显表达变化的miRNAs。在这些miRNAs里,大约有1/3的miRNAs被预测可以靶向调控AA代谢通路相关的基因。我们也研究了已知单核苷酸多态性(single nucleotide polymorphisms,SNPs)在扩张型心肌病并发心力衰竭患者中差异表达的miRNAs序列中的分布,发现在种子区域或整个序列上具有较多SNPs的miRNAs。以上这些结果可为未来研究miRNAs在扩张型心肌病并发心力衰竭发病机理中的功能提供线索。

Heart failure(HF),a clinical syndrome with high morbidity and mortality,is becoming a growing public health problem.Dilated cardiomyopathy(DCM)is one of the major causes of HF,yet the molecular mechanisms underlying DCM-mediated HF are not completely understood.Previous studies have shown that dysregulation of arachidonic acid(AA)metabolism could contribute to the development of HF.To explore the roles of microRNAs(miRNAs)in regulating AA metabolism in HF,we used two public datasets to analyze the expression changes of miRNAs in the patients of DCM-mediated HF.A total of 101 and 88 miRNAs with significant abundance alterations in the two dataset were obtained,respectively.Around 1/3 of these miRNAs were predicted to target AA metabolic pathway genes.We also investigated the distribution of known single nucleotide polymorphisms(SNPs)within the sequences of mi RNAs dysregulated in DCM-mediated HF patients,and identified miRNAs harboring high number of SNPs in either the seed regions or the entire sequences.These information could provide clues for further functional studies of miRNAs in the pathogeny of DCM-mediated HF.