The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250012, PR China.
Institute of Endocrinology, Shandong Academy of Clinical Medicine, Shandong Clinical Medical Center of Endocrinology and Metabolism, Jinan, 250021, PR China.
Tissue Cell. 2020 Dec;67:101451. doi: 10.1016/j.tice.2020.101451. Epub 2020 Oct 21.
MicroRNAs (miRNAs) are reported to play pivotal roles in reactive oxygen species (ROS)-induced endothelial cell injury and several studies have demonstrated the miRNA distribution in the mitochondria of various cells. However, very little is known about its changes and roles in ROS-induced endothelial cell injury. In the present study, we systematically revealed the distribution changes of miRNAs in mitochondria during ROS-induced endothelial cell injury and found that HO obviously reduced the mitochondrial distribution of many miRNAs without affecting their expression levels in the whole endothelial cells. Most of these miRNAs showing reduced mitochondrial distribution were potentially involved in ROS-induced endothelial cell injury. MiR-381-3p was a typical representative of these miRNAs and its redistribution between mitochondria and cytosol regulated the network consisting of downstream molecules (P53, P21, CCND1, and MYC) by inhibiting its target genes (LRP6 and NFIA) to promote apoptosis and inhibit proliferation in endothelial cells. Our findings highlight the significance of redistribution of miRNAs between mitochondria and cytosol and improve our understanding of miRNA function regulation.
微小 RNA（miRNAs）被报道在活性氧（ROS）诱导的内皮细胞损伤中发挥关键作用，并且有几项研究已经证明了 miRNA 在各种细胞的线粒体中的分布。然而，对于其在 ROS 诱导的内皮细胞损伤中的变化和作用知之甚少。在本研究中，我们系统地揭示了 ROS 诱导的内皮细胞损伤过程中线粒体中 miRNA 的分布变化，并且发现 HO 明显减少了许多 miRNA 的线粒体分布，而不影响其在整个内皮细胞中的表达水平。这些显示线粒体分布减少的 miRNA 大多可能参与了 ROS 诱导的内皮细胞损伤。miR-381-3p 是这些 miRNA 中的一个典型代表，其在线粒体和细胞质之间的重新分布通过抑制其靶基因（LRP6 和 NFIA）来调节下游分子（P53、P21、CCND1 和 MYC）组成的网络，从而促进内皮细胞凋亡并抑制增殖。我们的研究结果强调了 miRNA 在线粒体和细胞质之间重新分布的重要性，并提高了我们对 miRNA 功能调节的认识。
