Inhibition of miR-134 Protects Against Hydrogen Peroxide-Induced Apoptosis in Retinal Ganglion Cells.
MicroRNAs (miRNAs) have been suggested to play an important role in neurological diseases. Particularly, miR-134 is reportedly involved in regulating neuron survival. However, the association between miR-134 and retinal ganglion cell (RGC) survival under adverse stimulus has not been extensively investigated. In this study, we aimed to explore the role and underlying mechanism of miR-134 in regulating RGC apoptosis in response to hydrogen peroxide (H2O2) treatment. Results showed that the expression of miR-134 dose- and time-dependently increased in RGC after H2O2 treatment. H2O2-induced RGC apoptosis was significantly attenuated by the inhibition of miR-134 expression by antagomiR-134 and was enhanced by miR-134 overexpression. Luciferase reporter assay revealed a direct interaction between miR-134 and the 3'-untranslated region of cyclic AMP-response element-binding protein (CREB), a critical transcription factor for neuronal protection. In H2O2-treated RGCs, the inhibition of miR-134 significantly elevated the expression of CREB and its downstream genes, including brain-derived neurotrophic factor (BDNF) and Bcl-2. Furthermore, the inhibition of miR-134 also increased the expression of miR-132, a rapid response gene downstream of CREB. In addition, the target gene of miR-132, acetylcholinesterase was expectedly decreased by miR-134 inhibition. However, the overexpression of miR-134 exerted an opposite effect. The knockdown of CREB apparently abolished the protective effect of miR-134 inhibition against H2O2-induced RGC apoptosis. The increased expression of BDNF and Bcl-2 induced by miR-134 inhibition was also abrogated by CREB knockdown. Overall, our results suggested that the downregulation of miR-134 can effectively protect against H2O2-induced RGC apoptosis by negatively modulating CREB expression.
Department of Ophthalmology, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, 330006, China.
Yi
Y
Shao
Yao
Y
Yu
Qiong
Q
Zhou
Cheng
C
Li
Lu
L
Yang
Chong-Gang
CG
Pei
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009841:Oligonucleotides / Q000494:pharmacology; D018384:Oxidative Stress; D051381:Rats; D012165:Retinal Ganglion Cells / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; C581995:MIRN134 microRNA, rat; D035683:MicroRNAs; D009841:Oligonucleotides; D006861:Hydrogen Peroxide; D000110:Acetylcholinesterase