• World Neurosurg · Mar 2021

    LncRNA SOX2OT knockdown alleviates lipopolysaccharide-induced damage of PC12 cells by regulating miR-331-3p/Neurod1 axis.

    • Ronggang Li, Xiaofeng Li, Yong Huang, Haiying Qiu, Linlin Li, and Zhenggang Bi.
    • Department of Orthopedic Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
    • World Neurosurg. 2021 Mar 1; 147: e293-e305.

    BackgroundLong noncoding RNAs (lncRNAs) serve as crucial regulators in the pathogenesis of spinal cord injury (SCI). However, the role of lncRNA SOX2 overlapping transcript (SOX2OT) in SCI remains to be well revealed.MethodsAn SCI rat model was established and assessed by the Basso-Beattie-Bresnahan (BBB) method. An SCI PC12 cell model was established through lipopolysaccharide (LPS) treatment. Quantitative real-time polymerase chain reaction assay was used for SOX2OT, miR-331-3p, and neurogenic differentiation 1 (Neurod1) mRNA levels. Cell counting kit-8 assay and flow cytometry analysis were performed for cell viability and apoptosis, respectively. Enzyme-linked immunosorbent assay was performed for the levels of inflammatory cytokines. The production of superoxide dismutase and malondialdehyde was determined with relevant kits. Dual-luciferase reporter and RNA immunoprecipitation assays were conducted for the relationships among SOX2OT, miR-331-3p, and Neurod1. Western blot assay was employed for protein levels.ResultsSOX2OT was elevated in SCI rat and cell models. SOX2OT knockdown relieved the injury of SCI in SCI rat model. Moreover, the suppressive role in PC12 cell viability and the promotional roles in apoptosis, inflammation, and oxidative stress mediated by LPS were all restored by silencing SOX2OT. For mechanism analysis, SOX2OT was identified as a sponge of miR-331-3p to positively regulate Neurod1 expression. Inhibition of miR-331-3p reversed the effect of SOX2OT knockdown on LPS-induced PC12 damage. Overexpression of miR-331-3p protected PC12 cells from LPS-induced damage by binding to Neurod1. In addition, SOX2OT knockdown relieved PC12 cell injury by inactivation of Janus kinase-signal transducer and activator of transcription pathway.ConclusionsSOX2OT promoted PC12 cell injury through modulating miR-331-3p/Neurod1 axis and activating Janus kinase-signal transducer and activator of transcription pathway.Copyright © 2020 Elsevier Inc. All rights reserved.

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