a Department of Medicine Cardiovascular, Luoyang Central Hospital Affiliated to Zhengzhou University , Luoyang , Henan , China.
b Institute of Cardiovascular Research, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine , Shanghai , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3013-3020. doi: 10.1080/21691401.2019.1640232.
This research planned to dig the impacts and potential principles of long noncoding RNA RP4 onH9c2 cell injury induced by hypoxia. The H9c2 cardiac muscle cells were cultured under 3% O concentration to induce hypoxia injury, followed by detection of RP4 expression. RP4 was then overexpressed and silenced to investigate its effects on cell injury induced by hypoxia. The potential correlation between RP4 and miR-939, between miR-939 and Bnip3, and between RP4/miR-939/Bnip3 axis and Wnt/β-catenin pathway activation were explored. Biological processes (suppressed cell viability, migration and invasion, but enhanced cell apoptosis) were changed by hypoxia. Upregulation of RP4 enhanced hypoxia-produced damage in H9c2 cells. Additionally, miR-939 expression was opposite regulated by RP4, and miR-939 mimic abrogated the influences of pc-RP4 on enhanced hypoxia damage in H9c2 cells. Moreover, Bnip3 was targeted by miR-939 and their correlation is negative. Furthermore, upregulation of RP4 exacerbated hypoxia-produced injury in H9c2 cells by sensitizing Wnt/β-catenin signals in H9c2 cells, which was regulated by miR-939/Bnip3 axis. Our findings reveal that RP4 is highly expressed in the hypoxia-resulted H9c2 cells. Enhanced expression of RP4 may exacerbate hypoxia injury in cardiomyocytes through regulating miR-939/Bnip3 axis-mediated briskness of Wnt/β-catenin signals. Our study will offer a fresh theoretical basis for the treatment of ischemic myocardial injury.
这项研究旨在探讨长链非编码 RNA RP4 对低氧诱导的 H9c2 细胞损伤的影响和潜在机制。将 H9c2 心肌细胞置于 3% O2浓度下培养以诱导低氧损伤，然后检测 RP4 的表达。接着过表达和沉默 RP4，以研究其对低氧诱导的细胞损伤的影响。探讨了 RP4 与 miR-939 之间、miR-939 与 Bnip3 之间以及 RP4/miR-939/Bnip3 轴与 Wnt/β-catenin 通路激活之间的潜在相关性。低氧导致生物学过程（抑制细胞活力、迁移和侵袭，增强细胞凋亡）发生改变。RP4 的上调增强了低氧诱导的 H9c2 细胞损伤。此外，RP4 反向调节 miR-939 的表达，miR-939 模拟物可消除 pc-RP4 对增强的低氧损伤的影响。此外，miR-939 靶向 Bnip3，且二者呈负相关。此外，RP4 的上调通过敏化 H9c2 细胞中的 Wnt/β-catenin 信号，加剧了低氧诱导的 H9c2 细胞损伤，这是由 miR-939/Bnip3 轴调节的。我们的研究结果表明，在低氧诱导的 H9c2 细胞中，RP4 表达上调。增强 RP4 的表达可能通过调节 miR-939/Bnip3 轴介导的 Wnt/β-catenin 信号的敏感性，加剧心肌细胞的低氧损伤。我们的研究为缺血性心肌损伤的治疗提供了新的理论基础。
