Department of Anesthesia, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Department of Emergency, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, Jiangsu 223002, China.
Biomed Pharmacother. 2017 Oct;94:394-401. doi: 10.1016/j.biopha.2017.07.083. Epub 2017 Aug 1.
Increasing study has suggested that microRNAs (miRNAs) are pivotal regulators in regulating hypoxia-induced injury. miR-142-5p has been suggested as a critical regulator for cellular survival. However, the role of miR-142-5p in regulating hypoxia-induced injury remains unknown. In this study, we aimed to investigate the mechanistic roles of miR-142-5p in regulating cell survival during hypoxia treatment using H9C2 cardiomyoblasts and primary cardiomyocytes. We showed that miR-142-5p expression level was significantly repressed by hypoxia treatment. Overexpression of miR-142-5p during hypoxia induced extensive cell injury and apoptosis whereas suppression of miR-142-5p significantly promoted cell viability and attenuated cell apoptosis with hypoxia treatment. Sirtuin7 (SIRT7) was identified as a direct target gene of miR-142-5p by bioinformatics analysis and dual-luciferase reporter assays. Overexpression of miR-142-5p significantly decreased SIRT7 expression, while suppression of miR-142-5p increased SIRT7 expression. Furthermore, overexpression of SIRT7 protected H9C2 cardiomyoblasts and primary cardiomyocytes against hypoxia-induced injury and apoptosis. The silencing of SIRT7 markedly abrogated the protective effect induced by miR-142-5p suppression. Taken together, these results suggest that downregulation of miR-142-5p alleviates hypoxia-induced injury through upregulation of SIRT7. Our study suggests miR-142-5p/SIRT7 as potential therapeutic targets for ischemic heart disease.
越来越多的研究表明，微小 RNA（miRNAs）是调节低氧诱导损伤的关键调节剂。miR-142-5p 被认为是细胞存活的关键调节剂。然而，miR-142-5p 在调节低氧诱导损伤中的作用尚不清楚。在这项研究中，我们旨在使用 H9C2 心肌细胞和原代心肌细胞研究 miR-142-5p 在调节低氧处理期间细胞存活中的机制作用。结果表明，miR-142-5p 的表达水平在低氧处理时显著受到抑制。低氧处理时 miR-142-5p 的过表达诱导广泛的细胞损伤和凋亡，而 miR-142-5p 的抑制显著促进细胞活力并减轻低氧处理引起的细胞凋亡。通过生物信息学分析和双荧光素酶报告基因实验，鉴定 Sirtuin7（SIRT7）为 miR-142-5p 的直接靶基因。miR-142-5p 的过表达显著降低 SIRT7 的表达，而 miR-142-5p 的抑制增加 SIRT7 的表达。此外，SIRT7 的过表达可保护 H9C2 心肌细胞和原代心肌细胞免受低氧诱导的损伤和凋亡。SIRT7 的沉默显著削弱了由 miR-142-5p 抑制诱导的保护作用。综上所述，这些结果表明，miR-142-5p 的下调通过上调 SIRT7 缓解低氧诱导的损伤。我们的研究表明，miR-142-5p/SIRT7 可能成为缺血性心脏病的潜在治疗靶点。
