Wang Wu M, Lu Gang, Su Xian W, Lyu Hao, Poon Wai S
Division of Neurosurgery, Department of Surgery, Prince of Wales HospitalThe Chinese University of Hong Kong, Hong Kong, China.
Front Cell Neurosci. 2017 Apr 10;11:96. doi: 10.3389/fncel.2017.00096. eCollection 2017.
MicroRNAs are implicated in neuronal development and maturation. Neuronal maturation, including axon outgrowth and dendrite tree formation, is regulated by complex mechanisms and related to several neurodevelopmental disorders. We demonstrated that one neuron-enriched microRNA, microRNA-182 (miR-182), played a significant role in regulating neuronal axon outgrowth and dendrite tree formation. Overexpression of miR-182 promoted axon outgrowth and complexity of the dendrite tree while also increasing the expression of neurofilament-M and neurofilament-L, which provide structural support for neurite outgrowth. However, a reduction of miR-182 inhibited neurite outgrowth. Furthermore, we showed that miR-182 activated the AKT pathway by increasing AKT phosphorylation on S473 and T308 and inhibiting PTEN activity by increasing phosphorylation on S380. Inhibition of AKT activity with the PI3-K inhibitor LY294002 could downregulate AKT and PTEN phosphorylation and suppress axon outgrowth. In addition, we showed that might be the target of miR-182 that takes part in the regulation of neuronal maturation; blockage of endogenous BCAT2 promotes axon outgrowth and AKT activity. These observations indicate that miR-182 regulates axon outgrowth and dendrite maturation involving activation of the PTEN/AKT pathway.
微小RNA与神经元的发育和成熟有关。神经元的成熟，包括轴突生长和树突树形成，受复杂机制调控，且与多种神经发育障碍相关。我们证明，一种在神经元中高表达的微小RNA，即微小RNA - 182（miR - 182），在调节神经元轴突生长和树突树形成中发挥重要作用。miR - 182的过表达促进轴突生长和树突树的复杂性，同时还增加了神经丝-M和神经丝-L的表达，它们为神经突生长提供结构支持。然而，miR - 182的减少会抑制神经突生长。此外，我们发现miR - 182通过增加AKT在S473和T308位点的磷酸化来激活AKT信号通路，并通过增加S380位点的磷酸化来抑制PTEN活性。用PI3 - K抑制剂LY294002抑制AKT活性可下调AKT和PTEN的磷酸化并抑制轴突生长。另外，我们表明 可能是参与神经元成熟调节的miR - 182的靶标；内源性BCAT2的阻断促进轴突生长和AKT活性。这些观察结果表明，miR - 182通过激活PTEN/AKT信号通路来调节轴突生长和树突成熟。
