LINC00665 rescues bupivacaine induced neurotoxicity in human neural cell of SH-SY5Y through has-miR-34a-5p

Abstract Background Excessive application of local anesthetics, bupivacaine (BUP) may induce neurotoxicity and lead to neurologic dysfunctions in human brains. Yet, the exact molecular mechanisms underlying BUP-induced neurotoxicity was not fully understood. In this study, we utilized an in vitro SH‐SY5Y cell culture model to explore the functional mechanism of long intergenic non-protein coding RNA 665 (LINC00665) in regulating BUP-induced neurotoxicity. Methods SH‐SY5Y cells were induced with BUP in vitro, and their viability and apoptosis were monitored. BUP-induced LINC00665 expression was also monitored, by qRT-PCR. LINC00665 was then overexpressed in SH‐SY5Y cells, and its effects on BUP-induced neurotoxicity were investigated. The downstream target transcript of LINC00665, human mature microRNA-34a-5p (hsa-miR-34a-5p) was investigated in BUP-induced SH‐SY5Y cells. Co-regulation of LINC00665 / hsa-miR-132–3p epigenetic axis was further examined on BUP-induced apoptosis in SH‐SY5Y cells. Results BUP reduced cell viability, induced apoptosis and downregulated LINC00665 in SH‐SY5Y cells. LINC00665 overexpression rescued BUP-induced neurotoxicity in SH‐SY5Y cells. Hsa-miR-34a-5p expression was directly correlated with BUP treatment and LINC00665 overexpression in SH‐SY5Y cells. Upregulating hsa-miR-34a-5p reversed the rescuing effects of LINC00665 on BUP-induced SH‐SY5Y apoptosis. Conclusions BUP-induced neurotoxicity in human neural cells may be regulated by the epigenetic axis of LINC00665 / hsa-miR-34a-5p.