Long non-coding RNA uc.217 regulates neurite outgrowth in dorsal root ganglion neurons following peripheral nerve injury

摘要

The intrinsic regeneration capacity of dorsal root ganglion (DRG) neurons can be activated after sciatic nerve injury, and peripheral nerve regeneration is a complex process regulated by multiple molecular responses and signaling pathways. Long non-coding RNAs (lncRNAs) are RNA transcripts >200 nucleotides in length without protein-coding potential. They regulate gene expression at epigenetic, transcriptional and post-transcriptional levels, and are thus involved in many biological processes and human diseases. However, the role and mechanisms of lncRNAs in regulating the responses of DRG neurons to sciatic nerve injury are not fully investigated. We have previously analysed the expression profiles of lncRNAs and mRNAs in L4-6 DRGs, following rat sciatic nerve transection, by microarray analysis, and constructed a coexpression network of dysregulated lncRNAs and coding genes. In this study, one of these dysregulated lncRNAs, uc.217, was chosen for detailed examination of its expression changes and regulative functions in regenerative DRG neuronal outgrowth. Quantitative real-time PCR and insitu hybridisation confirmed that the expression of uc.217 was down-regulated in DRG neurons after sciatic nerve injury. Silencing of uc.217 expression by small interfering RNA could significantly promote neurite outgrowth in cultured DRG neurons. Moreover, bioinformatic analysis and experimental validation were performed to identify several potential targets of uc.217, which were involved in the regulation of DRG neuron outgrowth. Collectively, our results suggested that a new lncRNA, uc.217, played an important regulative role in peripheral nerve regeneration.