Abstract
Cerebral ischemia–reperfusion (I/R) injury is the common symptom of ischemic stroke, which poses a heavy burden to human health. Long non-coding RNA (lncRNA) is indicated to be a critical regulator in cerebral ischemia. This study aims to reveal the effects of lncRNA small nucleolar RNA host gene 15 (SNHG15) on oxygen–glucose deprivation and reoxygenation (OGD/R)-induced neuron injury and underlying mechanism. The expression levels of SNHG15, microRNA-455-3p (miR-455-3p) and tumour protein p53 inducible nuclear protein 1 (TP53INP1) mRNA were determined by quantitative real time polymerase chain reaction in P12 cells. The protein levels of TP53INP1, cleaved caspase-3, caspase-3, B-cell lymphoma-2 and BCL2-associated x protein (Bax) were detected by western blot in P12 cells. Cell viability and apoptosis were revealed by cell counting kit-8 assay and flow cytometry analysis, respectively, in P12 cells. Caspase-3 activity, the levels of tumor necrosis factor-α and interleukin-1β and the production of reactive oxygen species (ROS) were severally determined by caspase-3 activity assay, Enzyme-linked immunosorbent assay and ROS detection assay in P12 cells. The binding relationship between miR-455-3p and SNHG15 or TP53INP1 was predicted by starbase online database, and identified by dual-luciferase reporter, RNA pull-down or RNA immunoprecipitation assay. SNHG15 expression and the mRNA and protein levels of TP53INP1 were dramatically upregulated, while miR-455-3p expression was apparently downregulated in OGD/R-induced PC12 cells. SNHG15 silencing hindered the effects of OGD/R treatment on cell viability, apoptosis, inflammation and oxidative in PC12 cells; however, these impacts were restored after miR-455-3p inhibitor transfection. Additionally, SNHG15 acted as a sponge of miR-455-3p and miR-455-3p bound to TP53INP1. SNHG15 contributed to OGD/R-induced neuron injury by regulating miR-455-3p/TP53INP1 axis, which provided a novel insight to study lncRNA-directed therapy in ischemia stoke.
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Fan, Y., Wei, L., Zhang, S. et al. LncRNA SNHG15 Knockdown Protects Against OGD/R-Induced Neuron Injury by Downregulating TP53INP1 Expression via Binding to miR-455-3p. Neurochem Res 46, 1019–1030 (2021). https://doi.org/10.1007/s11064-020-03222-9
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DOI: https://doi.org/10.1007/s11064-020-03222-9