Department of Biology, Science and Research branch, Islamic Azad University, Tehran, Iran.
Cardiogenetic Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
J Clin Lab Anal. 2022 Apr;36(4):e24252. doi: 10.1002/jcla.24252. Epub 2022 Feb 14.
Evidence indicates that the dysregulation of extracellular matrix (ECM) components can lead to cardiovascular diseases. The Talin-1 (TLN1) gene is a major component of the ECM, and it mediates integrin adhesion to the ECM. In this study, we aimed to determine microRNAs (miRs) that regulate the expression of TLN1 and determine expression alterations in TLN1 and its targeting miRs in coronary artery disease (CAD).
Data sets of CAD and normal samples of blood exosomes were downloaded, and TLN1 was chosen as one of the genes with differential expressions in an in silico analysis. Next, miR-182-5p and miR-9-5p, which have a binding site on 3´-UTR of TLN1, were selected using bioinformatics tools. Then, the miR target site was cloned in the psiCHECK-2 vector, and direct interaction between the miR target site and the TLN1 3'-UTR putative target site was investigated by luciferase assay. The expression of miR-182-5p, miR-9-5p, and TLN1 in the serum samples of CAD and non-CAD individuals was assessed via a real-time quantitative polymerase chain reaction.
Our data revealed that miR-182-5p directly regulated the expression of TLN1. Moreover, miR-182-5p and miR-9-5p were significantly upregulated in the CAD group. Hence, both bioinformatics and experimental analyses determined the downregulated expression of TLN1 in the CAD samples.
Our findings demonstrated that miR-182-5p and miR-9-5p could play significant roles in TLN1 regulation and participate in CAD development by targeting TLN1. These findings introduce novel biomarkers with a potential role in CAD pathogenesis.
有证据表明,细胞外基质(ECM)成分的失调可导致心血管疾病。Talin-1(TLN1)基因是 ECM 的主要成分之一,它介导整合素与 ECM 的黏附。在本研究中,我们旨在确定调节 TLN1 表达的 microRNAs(miRs),并确定冠心病(CAD)中 TLN1 及其靶向 miRs 的表达变化。
下载 CAD 和正常血外泌体样本数据集,并在计算机分析中选择 TLN1 作为差异表达的基因之一。接下来,使用生物信息学工具选择具有 TLN1 3'-UTR 结合位点的 miR-182-5p 和 miR-9-5p。然后,将 miR 靶位点克隆到 psiCHECK-2 载体中,并通过荧光素酶测定法研究 miR 靶位点与 TLN1 3'-UTR 假定靶位点之间的直接相互作用。通过实时定量聚合酶链反应评估 CAD 和非 CAD 个体血清样本中 miR-182-5p、miR-9-5p 和 TLN1 的表达。
我们的数据显示,miR-182-5p 可直接调节 TLN1 的表达。此外,miR-182-5p 和 miR-9-5p 在 CAD 组中显著上调。因此,生物信息学和实验分析均确定 CAD 样本中 TLN1 的表达下调。
我们的研究结果表明,miR-182-5p 和 miR-9-5p 可能通过靶向 TLN1 在 TLN1 调节中发挥重要作用,并参与 CAD 的发生。这些发现为 CAD 发病机制提供了潜在的新型生物标志物。