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MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway
Wu M Wang1, Gang Lu1, Xian W Su1
1Division of Neurosurgery, Department of Surgery, Prince of Wales HospitalThe Chinese University of Hong Kong, Hong Kong, China.
Abstract:
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 BCAT2 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.
Insights
MicroRNA-182 (miR-182) is crucial for neuronal development, promoting axon outgrowth and dendrite formation. It activates the AKT pathway, highlighting its role in neurodevelopment and potential in related disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- MicroRNAs regulate complex mechanisms in neuronal development and maturation.
- Neuronal maturation, including axon outgrowth and dendrite formation, is vital for brain function and linked to neurodevelopmental disorders.
Purpose of the Study:
- To investigate the role of neuron-enriched microRNA-182 (miR-182) in regulating neuronal axon outgrowth and dendrite tree formation.
- To elucidate the molecular pathways, including the PTEN/AKT pathway, involved in miR-182-mediated neuronal maturation.
Main Methods:
- Overexpression and reduction of miR-182 in neuronal cells.
- Analysis of neurofilament-M and neurofilament-L expression.
- Assessment of AKT and PTEN phosphorylation.
- Inhibition of AKT activity using LY294002.
- Investigation of BCAT2 as a potential miR-182 target.
Main Results:
- Overexpression of miR-182 promoted axon outgrowth and dendrite complexity, increasing neurofilament expression.
- Reduced miR-182 inhibited neurite outgrowth.
- miR-182 activated the AKT pathway by increasing AKT phosphorylation and inhibiting PTEN activity.
- Inhibition of AKT suppressed axon outgrowth.
- BCAT2 was identified as a potential target of miR-182, and its blockage promoted axon outgrowth and AKT activity.
Conclusions:
- miR-182 plays a significant role in regulating neuronal axon outgrowth and dendrite maturation.
- The PTEN/AKT pathway is involved in miR-182's regulation of neuronal development.
- miR-182 represents a potential therapeutic target for neurodevelopmental disorders.
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