Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
Department of Endocrinology, The Affiliated Hospital of Qingdao University, No. 16 of Jiangsu Road, Qingdao, 266003, China.
Cell Biol Toxicol. 2018 Dec;34(6):479-489. doi: 10.1007/s10565-018-9424-2. Epub 2018 Feb 26.
Oxidative stress and miRNAs have been confirmed to play an important role in neurological diseases. The study aimed to explore the underlying effect and mechanisms of miR-146a in HO-induced injury of PC12 cells. Here, PC12 cells were stimulated with 200 μM of HO to construct oxidative injury model. Cell injury was evaluated on the basis of the changes in cell viability, migration, invasion, apoptosis, and DNA damage. Results revealed that miR-146a expression was up-regulated in HO-induced PC12 cells. Functional analysis showed that down-regulation of miR-146a alleviated HO-induced cytotoxicity in PC12 cells. Dual-luciferase reporter and western blot assay verified that MCL1 was a direct target gene of miR-146a. Moreover, anti-miR-146a-mediated suppression on cell cytotoxicity was abated following MCL1 knockdown in HO-induced PC12 cells. Furthermore, MCL1 activated JAK/STAT signaling pathway and MCL1 overexpression attenuated HO-induced cytotoxicity in PC12 cells by JAK/STAT signaling pathway. In conclusion, this study suggested that suppression of miR-146a abated HO-induced cytotoxicity in PC12 cells via regulating MCL1/JAK/STAT pathway.
氧化应激和 microRNAs 已被证实在神经疾病中发挥重要作用。本研究旨在探讨 miR-146a 在 HO 诱导的 PC12 细胞损伤中的潜在作用及机制。在此，用 200 μM 的 HO 刺激 PC12 细胞构建氧化损伤模型。基于细胞活力、迁移、侵袭、凋亡和 DNA 损伤的变化来评估细胞损伤。结果表明，HO 诱导的 PC12 细胞中 miR-146a 的表达上调。功能分析表明，下调 miR-146a 可减轻 HO 诱导的 PC12 细胞毒性。双荧光素酶报告基因和 Western blot 实验验证了 MCL1 是 miR-146a 的直接靶基因。此外，在 HO 诱导的 PC12 细胞中敲低 MCL1 后，抗 miR-146a 介导的细胞毒性抑制作用减弱。此外，MCL1 激活了 JAK/STAT 信号通路，MCL1 过表达通过 JAK/STAT 信号通路减弱了 HO 诱导的 PC12 细胞的细胞毒性。综上所述，本研究表明，抑制 miR-146a 通过调节 MCL1/JAK/STAT 通路减轻了 HO 诱导的 PC12 细胞的细胞毒性。
