Effect of activation of the Akt/mTOR signaling pathway by EEF1A2 on the biological behavior of osteosarcoma

Yang, Jianing; Tang, Jun; Li, Juan; Cen, Ying; Chen, Junjie; Dai, Gengwu

doi:10.21037/atm-20-7974

Cited by 14 publications

(9 citation statements)

References 21 publications

(24 reference statements)

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“…1F ). Genes are mainly involved in the pathways including cAMP, ErbB, Rap1, and PI3K-Akt, and EEF1A2 was reported to activate the Akt/mTOR pathway [ 21 ]. Our result showed that EEF1A2 was poorly expressed in SCI (Fig.…”

Section: Resultsmentioning

confidence: 99%

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METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury

et al. 2022

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Spinal cord injury (SCI) is a devastating traumatic condition. METTL14-mediated m6A modification is associated with SCI. This study was intended to investigate the functional mechanism of RNA methyltransferase METTL14 in spinal cord neuron apoptosis during SCI. The SCI rat model was established, followed by evaluation of pathological conditions, apoptosis, and viability of spinal cord neurons. The neuronal function of primary cultured spinal motoneurons of rats was assessed after hypoxia/reoxygenation treatment. Expressions of EEF1A2, Akt/mTOR pathway-related proteins, inflammatory cytokines, and apoptosis-related proteins were detected. EEF1A2 was weakly expressed and Akt/mTOR pathway was inhibited in SCI rat models. Hypoxia/Reoxygenation decreased the viability of spinal cord neurons, promoted LDH release and neuronal apoptosis. EEF1A2 overexpression promoted the viability of spinal cord neurons, inhibited neuronal apoptosis, and decreased inflammatory cytokine levels. Silencing METTL14 inhibited m6A modification of EEF1A2 and increased EEF1A2 expression while METTL14 overexpression showed reverse results. EEF1A2 overexpression promoted viability and inhibited apoptosis of spinal cord neurons and inflammation by activating the Akt/mTOR pathway. In conclusion, silencing METTL14 repressed apoptosis of spinal cord neurons and attenuated SCI by inhibiting m6A modification of EEF1A2 and activating the Akt/mTOR pathway.

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Section: Resultsmentioning

confidence: 99%

“…The SCI rat model was initially established. Next, 20 genes with high correlation scores with SCI were identified, among which EEF1A2 can activate the Akt/mTOR pathway [ 21 ]. Our results showed decreased expressions of EEF1A2, p-Akt/Akt, and p-mTOR/mTOR in SCI rats.…”

Section: Discussionmentioning

confidence: 99%

METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury

et al. 2022

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“…From cancer studies, it was established that eEF1A proteins can promote cell growth and proliferation by serving as an upstream activator of PI3K/AKT/mTOR [ 13 , 42 ] and/or PI3K/AKT/STAT3 [ 14 , 15 ] pathways. In partial agreement with those in vitro studies, our results showed that in an in vivo model of CNS injury, the overexpression of eEF1A proteins elevated mTOR activity, whereas co-overexpressing both proteins had no synergistic effect.…”

Section: Discussionmentioning

confidence: 99%

Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury

et al. 2022

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Although protein synthesis is hypothesized to have a pivotal role in axonal repair after central nervous system (CNS) injury, the role of core components of the protein synthesis machinery has not been examined. Notably, some elongation factors possess non-canonical functions that may further impact axonal repair. Here, we examined whether overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins enhances the collateral sprouting of corticospinal tract (CST) neurons after unilateral pyramidotomy, along with the underlying molecular mechanisms. We found that overexpressing eEF1A proteins in CST neurons increased the levels of pS6, an indicator for mTOR activity, but not pSTAT3 and pAKT levels, in neuronal somas. Strikingly, overexpressing eEF1A2 alone, but neither eEF1A1 alone nor both factors simultaneously, increased protein synthesis and actin rearrangement in CST neurons. While eEF1A1 overexpression only slightly enhanced CST sprouting after pyramidotomy, eEF1A2 overexpression substantially enhanced this sprouting. Surprisingly, co-overexpression of both eEF1A1 and eEF1A2 led to a sprouting phenotype similar to wild-type controls, suggesting an antagonistic effect of overexpressing both proteins. These data provide the first evidence that overexpressing a core component of the translation machinery, eEF1A2, enhances CST sprouting, likely by a combination of increased protein synthesis, mTOR signaling and actin cytoskeleton rearrangement.

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“…From cancer studies, it was established that eEF1A proteins can promote cell growth and proliferation by serving as an upstream activator of PI3K/AKT/mTOR 12,41 and/or PI3K/AKT/STAT3 13,14 pathways. In partial agreement with those in vitro studies, our results showed that in an in vivo model of CNS injury, the overexpression of eEF1A proteins elevated mTOR activity, whereas co-overexpressing both proteins had no synergistic effect.…”

Section: Discussionmentioning

confidence: 99%

Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury

Romaus-Sanjurjo

Saikia

Kim

et al. 2022

Preprint

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Although protein synthesis is hypothesized to have a pivotal role in axonal repair after central nervous system (CNS) injury, the role of core components of the protein synthesis machinery has not been examined. Notably, some elongation factors possess non-canonical functions that may further impact axonal repair. Here, we examined whether overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins enhances the collateral sprouting of corticospinal tract (CST) neurons after unilateral pyramidotomy, along with the underlying molecular mechanisms. Compared with axonal regeneration from injured neurons, axonal sprouting from uninjured neurons occurs spontaneously after injury and may represent a more accessible form of axonal repair for clinical translation. We found that overexpressing eEF1A1, eEF1A2 or both proteins in CST neurons increased the levels of pS6, an indicator for mTOR activity, in neuronal somas. In contrast, the levels of pSTAT3 and pAKT were not increased. Strikingly, overexpressing eEF1A2 alone, but neither eEF1A1 alone nor both factors simultaneously, increased protein synthesis and actin rearrangement in CST neurons. While eEF1A1 overexpression only slightly enhanced CST sprouting across the midline into the denervated side in the cervical spinal after pyramidotomy, eEF1A2 overexpression substantially enhanced this sprouting. Surprisingly, co-overexpression of both eEF1A1 and eEF1A2 led to a sprouting phenotype similar to wild-type controls, suggesting an antagonistic effect of overexpressing both proteins. These data provide the first evidence that overexpressing a core component of the translation machinery, eEF1A2, enhances CST sprouting, likely by a combination of increased protein synthesis, mTOR signaling and actin cytoskeleton rearrangement.

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Effect of activation of the Akt/mTOR signaling pathway by EEF1A2 on the biological behavior of osteosarcoma

Cited by 14 publications

References 21 publications

METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury

METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury

Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury

Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury

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