Dexmedetomidine Protects PC12 Cells from Lidocaine-Induced Cytotoxicity Through Downregulation of COL3A1 Mediated by miR-let-7b.
Safety concerns of some local anesthetics, such as lidocaine, have been raised in recent years due to potential neurological impairment. Dexmedetomidine may protect humans from neurotoxicity, and miR-let-7b is activated by nerve injury; however, the roles of miR-let-7b and its target gene in lidocaine-induced cytotoxicity are not well known. Through bioinformatics and a luciferase reporter assay, COL3A1 was suggested as a direct target gene of miR-let-7b. Here, we confirmed by measuring mRNA and protein levels that miR-let-7b was downregulated and COL3A1 was upregulated in lidocaine-treated cells, an observation that was reversed by dexmedetomidine. Similar to miR-let-7b mimics or knockdown of COL3A1, dexmedetomidine treatment reduced the expression of COL3A1, suppressed cell apoptosis and cell migration/invasion ability, and induced cell cycle progression and cell proliferation in PC12 cells, effects that were reversed by the miR-let-7b inhibitor. Meanwhile, proteins involved in cell apoptosis, such as Bcl2 and caspase 3, were impacted as well. Taken together, dexmedetomidine may protect PC12 cells from lidocaine-induced cytotoxicity through miR-let-7b and COL3A1, while also increasing Bcl2 and inhibiting caspase 3. Therefore, miR-let-7b and COL3A1 might play critical roles in neuronal injury, and they are potential therapeutic targets.
['Wang|Qiong|Q|', 'She|Yingjun|Y|', 'Bi|Xiaobao|X|', 'Zhao|Baisong|B|', 'Ruan|Xiangcai|X|', 'Tan|Yonghong|Y|']
D058647:Adrenergic alpha-2 Receptor Agonists D000818:Animals D017209:Apoptosis D053148:Caspase 3 D002465:Cell Movement D049109:Cell Proliferation D024061:Collagen Type III D019295:Computational Biology D020927:Dexmedetomidine D005786:Gene Expression Regulation D017930:Genes, Reporter D008012:Lidocaine D008156:Luciferases D035683:MicroRNAs D018696:Neuroprotective Agents D009843:Oligoribonucleotides D016716:PC12 Cells D011485:Protein Binding D019253:Proto-Oncogene Proteins c-bcl-2 D034741:RNA, Small Interfering D051381:Rats D015398:Signal Transduction D061567:Voltage-Gated Sodium Channel Blockers
dexmedetomidine COL3A1 miR-let-7b local anesthetics lidocaine