MiR-204-5p Inhibits the Proliferation and Differentiation of Fetal Neural Stem Cells by Targeting Wingless-Related MMTV Integration Site 2 to Regulate the Ephrin-A2/EphA7 Pathway

Abstract

Neonatal hypoxic ischemic encephalopathy (HIE) is mainly resulted from perinatal asphyxia, which can be repaired by NSCs. miR-204-5p is claimed to impact the activity NSCs. Our research will probe the miR-204-5p function in oxygen-glucose deprivation (OGD)-treated NSCs. miR-204-5p level was enhanced and WNT2 level was reduced in HIE rats. Rat NSCs were stimulated with OGD condition under the managing of mimic or inhibitor of miR-204-5p. The declined cell viability, enhanced apoptosis, downregulated Tuj1 and GFAP levels, and shortened total neurite length were observed in OGD-treated NSCs, which were further aggravated by the mimic and rescued by the inhibitor of miR-204-5p. Furthermore, the inactivated WNT2 and Ephrin-A2/EphA7 signaling pathway in OGD-stimulated NSCs was further repressed by the mimic and rescued by the inhibitor of miR-204-5p. In addition, WNT2 was confirmed as the targeting of miR-204-5p. Lastly, the function of miR-204-5p mimic on the proliferation, apoptosis, differentiation, WNT2 and Ephrin-A2/EphA7 signaling pathway in OGD-stimulated NSCs was abolished by HLY78, an activator of Wnt signaling. Collectively, miR-204-5p repressed the growth and differentiation of fetal NSCs by targeting WNT2 to regulate the Ephrin-A2/EphA7 pathway.