Shanxi Medical University, Taiyuan 030001, Shanxi, China.
The Affiliated Cardiovascular Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Biomed Res Int. 2019 Jun 25;2019:1580982. doi: 10.1155/2019/1580982. eCollection 2019.
Cardiac hypertrophy mainly predicts heart failure and is highly linked with sudden loss of lives. MicroRNAs (miRNAs) play essential roles in the development of cardiac hypertrophy through binding to corresponding mRNA targets. In this study, in order to investigate the roles of two mature forms of miRNA-195, miR-195-3p, and miR-195-5p, and models of cardiac hypertrophy were established by applying angiotensin II (Ang II) to H9c2 cardiomyocytes and infusing chronic Ang II to mice, respectively. We found that miR-195-5p was evidently equally upregulated in the and studies of cardiac hypertrophy induced by Ang II. High expressed miR-195-5p could adequately promote hypertrophy, whereas the suppression of miR-195-5p prevented hypertrophy of H9c2 cardiomyocytes under Ang II treatment. Furthermore, the luciferase reporter system demonstrated that MFN2 and FBWX7 were target genes of miR-195-5p, which negatively regulated the expression of these two genes in H9c2 cells. By contrast, in both models, expression of miR-195-3p was only slightly changed without statistical significance. In addition, we observed a trend towards decreased expression of hypertrophic markers by overexpressing miR-195-3p in AngII-treated H9c2 cardiomyocytes . Taken together, our study indicates that miR-195-5p promotes cardiac hypertrophy via targeting MFN2 and FBXW7 and may provide promising therapeutic strategies for interfering cardiac hypertrophy.
心肌肥厚主要预测心力衰竭,与生命突然丧失高度相关。 microRNAs(miRNAs)通过与相应的 mRNA 靶标结合,在心肌肥厚的发展中发挥重要作用。在这项研究中,为了研究两种成熟形式的 miRNA-195(miR-195-3p 和 miR-195-5p)的作用,分别应用血管紧张素 II(Ang II)处理 H9c2 心肌细胞和慢性 Ang II 输注建立心肌肥厚模型。我们发现,miR-195-5p 在 Ang II 诱导的心肌肥厚的 和 研究中明显一致地上调。高表达的 miR-195-5p 可以充分促进心肌肥厚,而 miR-195-5p 的抑制可防止 Ang II 处理下 H9c2 心肌细胞的肥厚。此外,荧光素酶报告系统表明 MFN2 和 FBWX7 是 miR-195-5p 的靶基因,它们负调控这两个基因在 H9c2 细胞中的表达。相比之下,在两种模型中,miR-195-3p 的表达仅略有变化,无统计学意义。此外,我们观察到在 Ang II 处理的 H9c2 心肌细胞中过表达 miR-195-3p 时,肥厚标志物的表达呈下降趋势。综上所述,我们的研究表明 miR-195-5p 通过靶向 MFN2 和 FBXW7 促进心肌肥厚,并可能为干预心肌肥厚提供有前途的治疗策略。