Abstract
The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury. Therefore, identifying the key modulators of nerve regeneration may help improve axon regeneration and functional recovery after injury. Unlike for classical transcription factors and regeneration-associated genes, the function of long noncoding RNAs (lncRNAs) in the regulation of neuronal regeneration remains mostly unknown. In this study, we used RNA-Seq-based transcriptome profiling to analyze the expression patterns of lncRNAs and mRNAs in rat dorsal root ganglion (DRG) following sciatic nerve injury. Analyses using the lncRNA-mRNA co-expression network, gene ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes pathway databases indicated that the lncRNA Arrl1 decreases neurite outgrowth after neuronal injury. shRNA-mediated Arrl1 silencing increased axon regeneration both in vitro and in vivo and improved functional recovery of the sciatic nerve. Moreover, inhibiting an identified target gene of Arrl1, cyclin-dependent kinase inhibitor 2B (Cdkn2b), markedly promoted neurite outgrowth of DRG neurons. We also found that Arrl1 acts as a competing endogenous RNA that sponges a Cdkn2b repressor, microRNA-761 (miR-761), and thereby up-regulates Cdkn2b expression during neuron regeneration. We conclude that the lncRNA Arrl1 affects the intrinsic regeneration of DRG neurons by derepressing Cdkn2b expression. Our findings indicate a role for an lncRNA-microRNA-kinase pathway in the regulation of axon regeneration and functional recovery following peripheral nerve injury in rats.
Highlights
The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury
Our previous study indicated that the level of long non-coding RNA (lncRNA) was changed following sciatic nerve injury (SNI) in rat [14, 15], and recent research has reported that lncRNAs impacted the neuronal outgrowth by regulating regeneration-associated gene (RAG) expression [16]
We identified 895 differentially expressed mRNAs (Fig. 1B), including RAGs: Atf3 [17], GAP43 [18], Sox11 [19], and Gadd45a [20], the detail data of differentially expressed lncRNAs and mRNAs was available in Table S1 in the supporting information
Summary
The intrinsic regeneration ability of neurons is a pivotal factor in the repair of peripheral nerve injury. Our previous study indicated that the level of lncRNAs was changed following sciatic nerve injury (SNI) in rat [14, 15], and recent research has reported that lncRNAs impacted the neuronal outgrowth by regulating RAG expression [16]. QRT-PCR results indicated that Arrl1 expression was dramatically decreased in rat DRG post-SNI (Fig. 2A).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
