Role of Long Non-coding RNA in Nerve Regeneration.

Nerve injury can be caused by a variety of factors. It often takes a long time to repair a nerve injury and severe nerve injury is even difficult to heal. Therefore, increasing attention has focused on nerve injury and repair. Long non-coding RNA (lncRNA) is a newly discovered non-coding RNA with a wide range of biological activities. Numerous studies have shown that a variety of lncRNAs undergo changes in expression after nerve injury, indicating that lncRNAs may be involved in various biological processes of nerve repair and regeneration. Herein, we summarize the biological roles of lncRNAs in neurons, glial cells and other cells during nerve injury and regeneration, which will help lncRNAs to be better applied in nerve injury and regeneration in the future.

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves.

Our previous studies have shown that long noncoding RNA (lncRNA) H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration, and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons. However, the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear. In this study, we established a Sprague-Dawley rat model of sciatic nerve transection injury. We performed in situ hybridization and found that at 4-7 days after sciatic nerve injury, lncRNA H19 was highly expressed. At 14 days before injury, adeno-associated virus was intrathecally injected into the L4-L5 foramina to disrupt or overexpress lncRNA H19. After overexpression of lncRNA H19, the growth of newly formed axons from the sciatic nerve was inhibited, whereas myelination was enhanced. Then, we performed gait analysis and thermal pain analysis to evaluate rat behavior. We found that lncRNA H19 overexpression delayed the recovery of rat behavior function, whereas interfering with lncRNA H19 expression improved functional recovery. Finally, we examined the expression of lncRNA H19 downstream target SEMA6D, and found that after lncRNA H19 overexpression, the SEMA6D protein level was increased. These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves. This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.