MicroRNA-29a promotes the neural differentiation of rat neural stem/progenitor cells by targeting KLF4

Neural stem/progenitor cells (NSPCs) remain in the mammalian brain throughout life, where they have the ability to self-renew and generate different types of cell in the central nervous system (CNS). Therefore, NSPCs may be a potential novel therapeutic strategy following damage to the CNS. Previous research has reported that microRNA (miR)-29a served an important role in regulating cell proliferation, differentiation and survival; however, to the best of our knowledge, little is known of the effect of miR-29a in neural differentiation. The present study aimed to investigate the effect of miR-29a on the differentiation of NSPCs, determined via RNA interference, immunostaining, reverse transcription-quantitative PCR and western blotting. The present study discovered that the expression levels of miR-29a were significantly upregulated in a time-dependent manner during neural differentiation. Immunostaining showed that overexpression of miR-29a promoted neural differentiation, which manifested in increased expression levels of neuron-specific class III β-tubulin (Tuj1); however, miR-29a had no effect on neuroglial differentiation. The expression levels of Kruppel-like factor 4 (KLF4) were downregulated following overexpression of miR-29a, whereas the inhibition of miR-29a demonstrated the opposite effect. These results suggested that the overexpression of miR-29a may promote neural differentiation in cultured rat NSPCs by decreasing the expression levels of KLF4. Thus indicating that targeting KLF4, a crucial regulatory factor for the maintenance of stemness, may be a potential underlying mechanism of action for miR-29a. In conclusion, the findings of the present study identified a potential mechanism of action for miR-29a in NSPC differentiation and provided a novel insight into the treatment strategies for CNS damage.