The Transcription Factor TFCP2L1 is Associated with Myelination via miR708-5p Regulation in the Peripheral Nerve System

MicroRNAs (miRNAs) have been implicated in nerve injury and demyelination; however, their functions in peripheral nerves remain unclear. To determine the potential functions of miRNAs, an miRNA array was carried out. Here, miRNA array analysis of neuregulin-treated Schwann cells revealed 18 upregulated (> 2-fold) and 13 downregulated (> 2-fold) miRNAs. After sciatic nerve injury, miR708-5p was highly expressed in neuregulin-treated Schwann cells, whereas it was downregulated during postnatal development. A predicted functional interaction was found between miR708-5p and transcription factor CP2-like protein 1 (TFCP2L1) using a bioinformatics tool. This finding suggested that miR708-5p may regulate TFCP2L1. During sciatic nerve development, TFCP2L1 was upregulated on postnatal days 1 and 4, while it was downregulated after nerve axotomy and crush injury. Notably, TFCP2L1 was upregulated in cAMP-treated Schwann cells. We also found that activity of the myelin protein zero promoter was downregulated in TFCP2L1 siRNA-treated Schwann cells, whereas it was upregulated in TFCP2L1-overexpressing cells. Immunofluorescence analysis showed that TFCP2L1 was localized in Schwann cells. In addition, miR708-5p overexpression promoted migration of Schwann cells, while miR-708-5p inhibitor inhibited migration. miR708-5p inhibitor also blocked the migration of TFCP2L1 siRNA-treated Schwann cells. These findings indicate the functions of miR708-5p in TFCP2L1 regulation in the peripheral nervous system occur via regulation of Schwann cell migration.