Knockdown of lncRNA NKILA suppresses sevoflurane-induced neuronal cell injury partially by targeting miR-205-5p/ELAVL1 axis.

Abstract

Sevoflurane (Sev) is a wildly used volatile anesthetic agent that induces neurotoxicity. Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in Sev-induced neuronal injury. Here, we investigated the role of NF-kappaB-interacting lncRNA (NKILA) in Sev-treated human cortical neurons (HCN). From RT-qPCR, Sev dose-dependently increased HCN NKILA transcript expression. Neurotoxicity of Sev was detected using MTT, flow cytometry, Western blotting, and inflammatory mediator assays. Consequently, Sev reduced HCN viability and levels of Bcl-2, SOD, and GSH in HCN, and promoted HCN apoptosis rate and levels of cleaved-caspase-3, Bax, MDA, TNF-α, IL-6, and IL-1β. Silencing NKILA suppressed Sev-induced above effects. DIANA and starbase databases predicted the potential target relationship between miR-205-5p and NKILA or embryonic lethal abnormal vision-like 1 (ELAVL1); dual-luciferase and RIP confirmed these interactions. NKILA could increase ELAVL1 expression by regulating miR-205-5p. miR-205-5p overexpression and ELAVL1 knockdown could mimic effects of NKILA silencing in Sev-induced HCN. Deleting miR-205-5p and restoring ELAVL1 respectively abolished the neuroprotective effect of NKILA knockdown and miR-205-5p upregulation under Sev anesthesia. In conclusion, Sev induced neuronal cell apoptosis, inflammatory response and oxidative stress through NKILA/miR- 205-5p/ELAVL1 axis and caspase-3 and Bax/Bcl-2 pathway. Inhibiting NKILA might be a potential therapeutic strategy for Sev neurotoxicity.