Transcriptional Control of Peripheral Nerve Regeneration

Zhang, Yunsong; Zhao, Qian; Chen, Qianqian; Xu, Lingchi; Yi, Sheng

doi:10.1007/s12035-022-03090-0

Cited by 21 publications

(18 citation statements)

References 122 publications

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“…46,69,84 Activating transcription factor 3 is a transcriptional factor de novo upregulated after neuronal injury and associated with transcriptional reprogramming, regeneration, and TRPV1 activation. 9,68,101 This observation is in line with the ability for HNSCC-derived sEVs to induce neurite outgrowths 2,50,52 and suggests that cancer pain has a neuropathic component. 96 The upregulation of ATF3 in response to sEVs supports the idea that sEVs drastically impact neuronal gene expression to switch to a transcriptome facilitating axon elongation and neuronal sensitization.…”

Section: Discussionsupporting

confidence: 67%

HPV+ head and neck cancer–derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain

Inyang,

Evans,

Heussner

et al. 2023

Pain

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Severe pain is often experienced by patients with head and neck cancer and is associated with a poor prognosis. Despite its frequency and severity, current treatments fail to adequately control cancer-associated pain because of our lack of mechanistic understanding. Although recent works have shed some light of the biology underlying pain in HPV-negative oral cancers, the mechanisms mediating pain in HPV+ cancers remain unknown. Cancer-derived small extracellular vesicles (cancer-sEVs) are well positioned to function as mediators of communication between cancer cells and neurons. Inhibition of cancer-sEV release attenuated pain in tumor-bearing mice. Injection of purified cancer-sEVs is sufficient to induce pain hypersensitivity in naive mice that is prevented by QX-314 treatment and in Trpv1 −/− mice. Cancer-sEVs triggered calcium influx in nociceptors, and inhibition or ablation of nociceptors protects against cancer pain. Interrogation of published sequencing data of human sensory neurons exposed to human cancer-sEVs suggested a stimulation of protein translation in neurons. Induction of translation by cancer-sEVs was validated in our mouse model, and its inhibition alleviated cancer pain in mice. In summary, our work reveals that HPV+ head and neck squamous cell carcinoma–derived sEVs alter TRPV1+ neurons by promoting nascent translation to mediate cancer pain and identified several promising therapeutic targets to interfere with this pathway.

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Section: Discussionsupporting

confidence: 67%

HPV+ head and neck cancer–derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain

Inyang,

Evans,

Heussner

et al. 2023

Pain

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“…In addition, sox10, a key factor for peripheral nerve myelination, regulates pmp22 and MBP, which are markers of Schwann cell maturation. 33,34 It has been shown that demyelination can be improved by increasing the expression of sox10, krox20, MBP and pmp22. For example, Duman et al demonstrated that theophylline had beneficial effects on demyelination in a mouse model of peripheral neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Acer truncatum Bunge seed oil ameliorated oxaliplatin-induced demyelination by improving mitochondrial dysfunction via the Pink1/Parkin mitophagy pathway

Cheng,

Wang,

Guo

et al. 2024

Food Funct.

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“…Transcription factors play a crucial role in spinal cord injury. Recent studies have suggested that transcription factors, such as ATF3 [ 18 , 19 ], Sox11 [ 20 ], STAT3 [ 21 ], and Smad1 [ 22 – 24 ], are involved in axon regeneration, indicating their potential importance in neuronal functions. The current study aimed to investigate the effects of the transcription factor Ets1, which shows differential expression during spinal cord development, on the axonal growth of neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factor Ets1 Influences Axonal Growth via Regulation of Lcn2

Gu,

Li,

et al. 2023

Mol Neurobiol

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Transcription factors are essential for the development and regeneration of the nervous system. The current study investigated key regulatory transcription factors in rat spinal cord development via RNA sequencing. The hub gene Ets1 was highly expressed in the spinal cord during the embryonic period, and then its expression decreased during spinal cord development. Knockdown of Ets1 significantly increased the axonal growth of cultured spinal cord neurons. Luciferase reporter assays and chromatin immunoprecipitation assays indicated that Ets1 could directly bind to the Lcn2 promoter and positively regulate Lcn2 transcription. In conclusion, these findings provide the first direct evidence that Ets1 regulates axon growth by controlling Lcn2 expression, and Ets1 may be a novel therapeutic target for axon regeneration in the central nervous system.

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Transcriptional Control of Peripheral Nerve Regeneration

Cited by 21 publications

References 122 publications

HPV+ head and neck cancer–derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain

HPV+ head and neck cancer–derived small extracellular vesicles communicate with TRPV1+ neurons to mediate cancer pain

Acer truncatum Bunge seed oil ameliorated oxaliplatin-induced demyelination by improving mitochondrial dysfunction via the Pink1/Parkin mitophagy pathway

The Transcription Factor Ets1 Influences Axonal Growth via Regulation of Lcn2

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