Sohn Eun Jung, Nam Yun-Kyeong, Park Hwan Tae
Department of Molecular Neuroscience, Peripheral Neuropathy Research Center, College of Medicine, Dong-A University, Busan, South Korea.
Neuroreport. 2019 Feb 6;30(3):241-246. doi: 10.1097/WNR.0000000000001193.
Early growth response protein 2 (EGR2) is an essential transcription factor for peripheral nerve myelination. Schwann cells (SCs), the peripheral myelin-forming glial cells, express high levels of EGR2 during postnatal myelination. In contrast, SCs exhibit low EGR2 expression during Wallerian degeneration after injury. In this study, we screened 10 potential microRNAs (miRNAs) (20a-5p, 137-5p, 140-5p, 148b-3p, 150-5p, 17-5p, 93-5p, 20b-5p, 106b-5p, and 152-3p) that potentially target EGR2 using miRNA algorithms and identified that miRNAs 106b-5p, 140-5p, 93-5p, and 17-5p target EGR2 in SCs. These miRNAs directly target EGR2 by binding to the 3'-untranslated region to suppress EGR2 mRNA levels. Additionally, the levels of miRNAs 93-5p, 106b-5p, 17-5p, and 140-5p were decreased in the sciatic nerves during postnatal development; however, these miRNAs were increased on day 1 after sciatic nerve injury. Taken together, these findings suggest that the expression of EGR2 during postnatal development and Wallerian degeneration could be regulated by the inverse expression of miRNAs 106b-5p, 140-5p, 93-5p, and 17-5p, which target EGR2.
早期生长反应蛋白2（EGR2）是外周神经髓鞘形成所必需的转录因子。雪旺细胞（SCs）是外周形成髓鞘的神经胶质细胞，在出生后髓鞘形成过程中表达高水平的EGR2。相比之下，在损伤后的沃勒变性过程中，雪旺细胞的EGR2表达较低。在本研究中，我们使用miRNA算法筛选了10种可能靶向EGR2的潜在微小RNA（miRNA）（20a - 5p、137 - 5p、140 - 5p、148b - 3p、150 - 5p、17 - 5p、93 - 5p、20b - 5p、106b - 5p和152 - 3p），并确定miRNA 106b - 5p、140 - 5p、93 - 5p和17 - 5p在雪旺细胞中靶向EGR2。这些miRNA通过与3'非翻译区结合直接靶向EGR2，以抑制EGR2 mRNA水平。此外，在出生后发育过程中，坐骨神经中miRNA 93 - 5p、106b - 5p、17 - 5p和140 - 5p的水平降低；然而，在坐骨神经损伤后第1天，这些miRNA水平升高。综上所述，这些发现表明，在出生后发育和沃勒变性过程中，EGR2的表达可能受靶向EGR2的miRNA 106b - 5p、140 - 5p、93 - 5p和17 - 5p的反向表达调控。
