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Identifying potential functional lncRNAs in metabolic syndrome by constructing a lncRNA-miRNA-mRNA network.
Journal of Human Genetics ( IF 3.5 ) Pub Date : 2020-07-21 , DOI: 10.1038/s10038-020-0753-7
Dengju Yao 1 , Zijing Lin 2 , Xiaojuan Zhan 3 , Xiaorong Zhan 2
Affiliation  

The metabolic syndrome (MS) is a cluster of interrelated risk factors including diabetes mellitus, abdominal obesity, high cholesterol, and hypertension, which can significantly increase mortality and disability. Accumulating evidence suggest that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of human metabolic diseases. However, little is known about the regulatory role of lncRNAs in MS. In this work, we proposed a method for identifying potential MS-associated lncRNAs by constructing an lncRNA–miRNA–mRNA network (LMMN). Firstly, we constructed LMMN by integrating MS-associated genes, miRNA–mRNA interactions, miRNA–lncRNA interactions and mRNA/miRNA expression profiles in patients with MS. Then, we predicted potential MS-associated lncRNAs based on the topological properties of LMMN. As a result, we identified XIST as the most important lncRNA in LMMN. Furthermore, we focused on XIST/miR-214-3p and mir-181a-5p/PTEN axis and validated their expression in MS using real-time quantitative polymerase chain reaction (RT-qPCR). The RT-qPCR results showed that the expression of XIST and PTEN was significantly decreased (P < 0.05) while the expression of miR-214-3p was significantly increased (P < 0.05) in peripheral blood mononuclear cells (PBMCs) of patients with MS, compared with healthy controls. In addition, correlation analysis showed that XIST was negatively correlated with serum C peptide and PTEN was positively correlated with BMI of MS patients. Our findings provided new evidence for further exploring the regulatory role of XIST and other lncRNAs in MS.



中文翻译:

通过构建lncRNA-miRNA-mRNA网络来识别代谢综合征中潜在的功能性lncRNA。

代谢综合症(MS)是一系列相互关联的危险因素,包括糖尿病,腹部肥胖,高胆固醇和高血压,这会显着增加死亡率和致残率。越来越多的证据表明,长时间的非编码RNA(lncRNA)参与了人类代谢性疾病的发病机理。但是,对于lncRNA在MS中的调控作用知之甚少。在这项工作中,我们提出了一种通过构建lncRNA–miRNA–mRNA网络(LMMN)来识别与MS相关的lncRNA的方法。首先,我们通过整合MS患者的MS相关基因,miRNA–mRNA相互作用,miRNA–lncRNA相互作用以及mRNA / miRNA表达谱构建了LMMN。然后,我们基于LMMN的拓扑特性预测了潜在的与MS相关的lncRNA。结果是,我们将XIST确定为LMMN中最重要的lncRNA。此外,我们专注于XIST / miR-214-3p和mir-181a-5p / PTEN轴,并使用实时定量聚合酶链反应(RT-qPCR)验证了它们在MS中的表达。RT-qPCR结果显示XIST和PTEN的表达明显降低(P  <0.05),而的miR-214-3p的表达显著增加(P 在患有MS的外周血单核细胞(PBMC)<0.05),与健康对照相比。另外,相关分析表明,XIST与血清C肽呈负相关,PTEN与MS患者的BMI正相关。我们的发现为进一步探索XIST和其他lncRNA在MS中的调控作用提供了新的证据。

更新日期:2020-07-21
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