MicroRNA-29A/PTEN pathway modulates neurite outgrowth in PC12 cells

Zou, Hongjun; Ding, Yunchuan; Wang, Kui; Xiong, Erhui; Peng, Wan-Xin; Du, F.; Zhang, Z.; Liu, J.; Gong, Aihua

doi:10.1016/j.neuroscience.2015.01.055

Cited by 34 publications

(37 citation statements)

References 26 publications

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“…PTEN is a validated target of the miR-17-92 cluster, and its downstream PI3K/Akt/mTOR signaling pathway controls neurite remodeling 16, 25 , cell proliferation and differentiation 15, 26 . By employing Western blot, we measured protein level of PTEN and the phosphorylated downstream effectors in the IBZ.…”

Section: Resultsmentioning

confidence: 99%

“…Our present study only focused on the miR-17-92 cluster targeting the PTEN signaling pathway, since PTEN is a validated target of miR-17-92 cluster and the miR-17-92/PTEN axis controls neurite remodeling 16, 25 , cell proliferation and differentiation 15, 26 . Our previous in vitro data demonstrated that over-expression of the miR-17-92 cluster promoted axonal outgrowth of primary cortical neurons cultured in a microfluidic chamber, via down-regulating of PTEN and subsequent activation of the PI3K/Akt/mTOR signaling pathway 16 .…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA-17–92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats

Xin

Katakowski

Wang

et al. 2017

Stroke

462

350

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Background and Purpose Multipotent mesenchymal stromal cell (MSC) harvested exosomes are hypothesized as the major paracrine effectors of MSCs. In vitro, the miR-17-92 cluster promotes oligodendrogenesis, neurogenesis and axonal outgrowth. We therefore investigated whether the miR-17-92 cluster enriched exosomes (Exo-miR-17-92+) harvested from MSCs transfected with a miR-17-92 cluster plasmid enhance neurological recovery compared to control MSC derived exosomes (Exo-Con). Methods Rats subjected to 2 hours of transient middle cerebral artery occlusion (MCAO) were intravenously administered Exo-miR-17-92+, Exo-Con, or liposomes, and were sacrificed 28 days post MCAO. Histochemistry, immunohistochemistry and Golgi-Cox staining were used to assess dendritic, axonal, synaptic and myelin remodeling. Expression of phosphatase and tensin homolog (PTEN) and activation of its downstream proteins, protein kinase B (PKB or Akt), mechanistic target of rapamycin (mTOR), and glycogen synthase kinase 3 beta (GSK-3β) in the peri-infarct region were measured by means of Western blots. Results Compared with the liposome treatment, both exosome treatment groups exhibited significant improvement of functional recovery, but Ex-miR-17-92+ treatment had significantly more robust effects on improvement of neurological function, and enhancements of oligodendrogenesis, neurogenesis and neurite remodeling/neuronal dendrite plasticity in the ischemic boundary zone (IBZ) than the Ex-Con treatment. Moreover, Ex-miR-17-92+ treatment substantially inhibited PTEN, a validated miR-17-92 cluster target gene, and subsequently increased the phosphorylation of PTEN downstream proteins, Akt, mTOR and GSK-3β compared to Ex-Con treatment. Conclusions Our data suggest that treatment of stroke with tailored exosomes enriched with the miR-17-92 cluster increases neural plasticity and functional recovery after stroke, possibly via targeting PTEN to activate the PI3K/Akt/mTOR/GSK-3β signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

MicroRNA-17–92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats

Xin

Katakowski

Wang

et al. 2017

Stroke

462

350

View full text Add to dashboard Cite

show abstract

“…The PTEN/AKT pathway regulated by microRNAs plays important roles in neuronal maturation. MiR-9 and miR-124 regulate dendritic branching via AKT/GSK3β pathway (Xue et al, 2016); PTEN/miR-29a pathway modulates neurite outgrowth (Zou et al, 2015). In neuronal regeneration, PTEN/AKT pathway regulated by microRNA bantam enhances the regeneration of sensory neuron axons and dendrites (Song et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway

Wang

Lü

et al. 2017

Front. Cell. Neurosci.

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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.

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“…11 MiR-29a is involved in neural outgrowth through down-regulating PTEN and increasing Akt phosphorylation. 12 MiR-29 also promotes myogenesis by inhibiting YY1, a negative regulator of muscle genes. 10 High myopia is the second most common cause of blindness, owing to the increased risk of chorioretinal degeneration, premature cataracts, retinal detachment and glaucoma.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants in MiR-29a associated with high myopia

Xie

2016

Ophthalmic Genetics

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MicroRNA-29A/PTEN pathway modulates neurite outgrowth in PC12 cells

Cited by 34 publications

References 26 publications

MicroRNA-17–92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats

MicroRNA-17–92 Cluster in Exosomes Enhance Neuroplasticity and Functional Recovery After Stroke in Rats

MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway

Genetic variants in MiR-29a associated with high myopia

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