Let-7f promotes the differentiation of neural stem cells in rats

Hypoxic-ischemic brain damage (HIBD) is the major recognized perinatal cause of neurological morbidity in full-term new borns. Neural stem cells (NSCs) have been extensively studied because of their clinical applications in treating neuro degenerative diseases and brain injuries, including HIBD, while microRNAs (miRNAs) are deemed critical regulators of the proliferation and differentiation of NSCs. However, the role of let-7f in NSC differentiation remains unknown. Our study aims to investigate the role of let-7f in the differentiation of NSCs and brain development in rats and hence to explore the therapeutic potential of let-7f in the treatment of HIBD. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to assess the expressions of let-7f, and western blot was performed to detect GFAP, Tuj1 and Nestin in rat brains at postnatal day 1, 8 and 14 (n=12 per time point). The NSCs isolated from the brains of rat fetuses at gestational day 15 were transduced with lenti virus expressing let-7f or let-7f inhibitor so as to observe altered expressions of let-7f, GFAP, Tuj1 and Nestin. A gradually-increasing expression of let-7f was detected by qRT-PCR in rat brain tissues during postnatal brain development. Increased levels of GFAP and Tuj1, while a decreased level of Nestin, were detected by western blot in let-7f-overexpressing NSCs. In contrast, the cells expressing the let-7f inhibitor exhibited lower levels of GFAP and Tuj1, while a higher level of Nestin, compared with control cells. Therefore, let-7f is involved in brain development and promotes the differentiation of NSCs in rats.