Abstract
Nogo-66 can inhibit neurite outgrowth, while its regulation mechanisms have not been fully elucidated. Recent studies prove that lncRNAs are involved in neurite outgrowth. This study was aimed to investigate whether lncRNA FTX was involved in Nogo-66-induced inhibition of neurite outgrowth and explore the potential mechanism. The expression of relative genes was detected by qRT-PCR and western blot. The function of FTX was determined by overexpression and knockdown techniques. The interaction between FTX and PDK1 was evaluated by RIP and RNA pull-down assays. FTX expression was downregulated by Nogo-66 in PC12 cells. Nogo-66-induced inhibition of neurite outgrowth was relieved by FTX overexpression. FTX bound to PDK1 protein to disturb the interaction between PDK1 and E3 ubiquitin ligase RNF126, thereby blocked the ubiquitination degradation of PDK1 and elevated PDK1 protein level. Mechanically, FTX involved in the Nogo-66-induced inhibition of neurite outgrowth through the PDK1/PKB/GSK-3β pathway. In SCI rats, FTX knockdown inhibited neurite outgrowth induced by the receptor antagonist of Nogo-66. The present results suggested that FTX took part in Nogo-66-inhibited neurite outgrowth, and FTX exerted its function through regulating PDK1/PKB/GSK-3β pathway.