Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China and.
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China and
J Neurosci. 2018 Jul 18;38(29):6574-6585. doi: 10.1523/JNEUROSCI.3790-16.2018. Epub 2018 Jun 18.
As the major glia in PNS, Schwann cells play a critical role in peripheral nerve injury repair. Finding an efficient approach to promote Schwann cell activation might facilitate peripheral nerve repair. Long noncoding RNAs (lncRNAs) have been shown to regulate gene expression and take part in many biological processes. However, the role of lncRNAs in peripheral nerve regeneration is not fully understood. In this study, we obtained a global lncRNA portrayal following sciatic nerve injury in male rats using microarray and further investigated one of these dys-regulated lncRNAs, TNXA-PS1, confirming its vital role in regulating Schwann cells. Silencing TNAX-PS1 could promote Schwann cell migration and mechanism analyses showed that TNXA-PS1 might exert its regulatory role by sponging miR-24-3p/miR-152-3p and affecting dual specificity phosphatase 1 (Dusp1) expression. Systematic lncRNA expression profiling of sciatic nerve segments following nerve injury in rats suggested lncRNA TNXA-PS1 as a key regulator of Schwann cell migration, providing a potential therapeutic target for nerve injury repair. The PNS has an intrinsic regeneration capacity after injury in which Schwann cells play a crucial role. Therefore, further exploration of functional molecules in the Schwann cell phenotype modulation is of great importance. We have identified a set of dys-regulated long noncoding RNAs (lncRNAs) in rats following sciatic nerve injury and found that the expression of TNXA-PS1 was significantly downregulated. Mechanically analyses showed that TNXA-PS1 might act as a competing endogenous RNA to affect dual specificity phosphatase 1 (Dusp1) expression, regulating migration of Schwann cells. This study provides for the first time a global landscape of lncRNAs following sciatic nerve injury in rats and broadens the known functions of lncRNA during nerve injury. The investigation of TNXA-PS1 might facilitate the development of novel targets for nerve injury therapy.
作为 PNS 中的主要胶质细胞，许旺细胞在周围神经损伤修复中起着关键作用。寻找一种有效的方法来促进许旺细胞的激活可能有助于周围神经的修复。长链非编码 RNA（lncRNA）已被证明可以调节基因表达，并参与许多生物过程。然而，lncRNA 在周围神经再生中的作用尚未完全阐明。在这项研究中，我们使用微阵列技术获得了雄性大鼠坐骨神经损伤后的全基因组 lncRNA 图谱，进一步研究了这些失调的 lncRNA 之一 TNXA-PS1，证实了其在调节许旺细胞中的重要作用。沉默 TNAX-PS1 可以促进许旺细胞的迁移，机制分析表明，TNXA-PS1 可能通过海绵 miR-24-3p/miR-152-3p 并影响双特异性磷酸酶 1（Dusp1）的表达来发挥其调节作用。大鼠坐骨神经损伤后神经节段的系统 lncRNA 表达谱分析表明，lncRNA TNXA-PS1 是许旺细胞迁移的关键调节因子，为神经损伤修复提供了一个潜在的治疗靶点。周围神经系统在损伤后具有内在的再生能力，其中许旺细胞起着至关重要的作用。因此，进一步探索许旺细胞表型调节中的功能分子具有重要意义。我们已经确定了一组在大鼠坐骨神经损伤后失调的长链非编码 RNA（lncRNA），并发现 TNXA-PS1 的表达显著下调。机制分析表明，TNXA-PS1 可能作为竞争内源性 RNA 影响双特异性磷酸酶 1（Dusp1）的表达，调节许旺细胞的迁移。这项研究首次提供了大鼠坐骨神经损伤后 lncRNA 的全基因组图谱，并拓宽了 lncRNA 在神经损伤过程中的已知功能。对 TNXA-PS1 的研究可能有助于为神经损伤治疗开发新的靶点。
