Department of Human Anatomy, Institute of Neurobiology, Nantong University, Nantong, China.
Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
J Cell Mol Med. 2022 May;26(9):2717-2727. doi: 10.1111/jcmm.17285. Epub 2022 Apr 16.
In the adult mammalian brain, neural stem cells (NSCs) are the precursor cells of neurons that contribute to nervous system development, regeneration, and repair. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cell fate determination and differentiation by negatively regulating gene expression. Here, we identified a post-transcriptional mechanism, centred around miR-130a-3p that regulated NSC differentiation. Importantly, overexpressing miR-130a-3p promoted NSC differentiation into neurons, whereas inhibiting miR-130a-3p function reduced the number of neurons. Then, the quantitative PCR, Western blot and dual-luciferase reporter assays showed that miR-130a-3p negatively regulated acyl-CoA synthetase long-chain family member 4 (Acsl4) expression. Additionally, inhibition of Acsl4 promoted NSC differentiation into neurons, whereas silencing miR-130a-3p partially suppressed the neuronal differentiation induced by inhibiting Acsl4. Furthermore, overexpressing miR-130a-3p or inhibiting Acsl4 increased the levels of p-AKT, p-GSK-3β and PI3K. In conclusion, our results suggested that miR-130a-3p targeted Acsl4 to promote neuronal differentiation of NSCs via regulating the Akt/PI3K pathway. These findings may help to develop strategies for stem cell-mediated treatment for central nervous system diseases.
在成年哺乳动物大脑中，神经干细胞（NSCs）是神经元的前体细胞，有助于神经系统的发育、再生和修复。微小 RNA（miRNA）是一种小的非编码 RNA，通过负向调控基因表达来调节细胞命运决定和分化。在这里，我们确定了一个以 miR-130a-3p 为中心的转录后机制，该机制调节 NSC 分化。重要的是，过表达 miR-130a-3p 促进 NSC 分化为神经元，而抑制 miR-130a-3p 功能则减少神经元的数量。然后，定量 PCR、Western blot 和双荧光素酶报告基因检测表明，miR-130a-3p 负向调节长链酰基辅酶 A 合成酶家族成员 4（Acsl4）的表达。此外，抑制 Acsl4 促进 NSC 分化为神经元，而沉默 miR-130a-3p 部分抑制了抑制 Acsl4 诱导的神经元分化。此外，过表达 miR-130a-3p 或抑制 Acsl4 增加了 p-AKT、p-GSK-3β 和 PI3K 的水平。总之，我们的结果表明，miR-130a-3p 通过调节 Akt/PI3K 通路靶向 Acsl4 促进 NSCs 的神经元分化。这些发现可能有助于开发基于干细胞的中枢神经系统疾病治疗策略。
