Inhibition of microRNA-429 attenuates oxygen–glucose deprivation/reoxygenation-induced neuronal injury by promoting expression of GATA-binding protein 4

MicroRNAs (miRNAs) have been documented as critical regulators in ischemia/reperfusion-induced neuronal death. A better understanding of miRNA-mediated molecular mechanisms in ischemia/reperfusion-induced neuronal death may provide therapeutic targets for cerebral ischemia/reperfusion injury. A growing body of evidence suggests that miR-429 is a apoptosis-related miRNA that is also induced by hypoxia. However, whether miR-429 is involved in regulating neuronal apoptosis during cerebral ischemia/reperfusion injury remains unclear. In this study, the effect of miR-429 on oxygen–glucose deprivation and reoxygenation (OGD/R)-induced neuronal injury was investigated in vitro. The results showed that miR-429 expression levels were upregulated in cultured neurons with OGD/R treatment. The downregulation of miR-429 significantly alleviated OGD/R-induced neuronal injury, whereas upregulation of miR-429 aggravated it. Bioinformatic analysis showed that miR-429 could directly target the 3′-untranslated region of GATA-binding protein 4 (GATA4), which was verified by dual-luciferase reporter assay. Moreover, we found that miR-429 negatively regulated GATA4 expression. Overexpression of GATA4 also significantly alleviated OGD/R-induced neuronal injury. However, knockdown of GATA4 partially reversed the protective effect induced by miR-429 downregulation. Overall, our data showed that downregulation of miR-429 protected neurons against OGD/R-induced injury by promoting GATA4 and suggested a potential therapeutic target for the treatment of cerebral ischemia/reperfusion injury. Correspondence to Jingye Hu, MM, Department of Trauma and Orthopaedics, The Yuncheng Central Hospital, No. 3690 Hedong Street, Yuncheng, Shanxi 044000, China Tel: +86 151 1044 8251; fax: +86 035 9639 6222; e-mail: hu_jingyejy@163.com Received February 28, 2018 Accepted March 7, 2018 © 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins

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