LncRNA OIP5-AS1 Mitigates Bupivacaine-Induced Neurotoxicity in Dorsal Root Ganglion Neurons Through Regulating NFAT5 Expression via Sponging miR-34b.

Abstract

Bupivacaine (BUP), which is widely used in anesthesia, can cause neurotoxicity and neurological abnormalities. This work intended to study the function of long non-coding RNA (lncRNA) OIP5 antisense RNA 1 (OIP5-AS1) in BUP-triggered neurotoxicity. OIP5-AS1, microRNA (miR)-34b, and nuclear factor of activated T cells 5 (NFAT5) levels were examined via real-time quantitative PCR (RT-qPCR). Cell proliferation, caspase-3 activity, and apoptosis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), caspase-3 activity, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays. The regulatory relationships between miR-34b and OIP5-AS1 or NFAT5 were validated via RNA binding protein immunoprecipitation (RIP) and dual-luciferase reporter assays. Our data demonstrated that OIP5-AS1 and NFAT5 levels were downregulated and miR-34b was upregulated upon exposure to BUP. Functional assays implied that the OIP5-AS1 deficiency impeded cell proliferation and enhanced the apoptosis of DRG neurons, while OIP5-AS1 addition reversed these changes. Moreover, OIP5-AS1 could bind to miR-34b and OIP5-AS1 regulated BUP-induced neurotoxicity via miR-34b. Besides, miR-34b could directly interact with NFAT5. Augmentation of miR-34b impeded cell proliferation and expedited the apoptosis and caspase-3 activity, while NFAT5 addition neutralized these impacts. Finally, it was verified that OIP5-AS1 could upregulate NFAT5 through sponging miR-34b. In sum, our results disclosed that OIP5-AS1 ameliorated BUP-caused neurotoxicity via regulating the miR-34b/NFAT5 axis, suggesting that OIP5-AS1 might be a promising therapeutic target for the treatment of BUP-induced neurotoxicity.