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Identification of epigenetic interactions between microRNA-30c-5p and DNA methyltransferases in neuropathic pain

Abstract: Neuropathic pain is a prevalent and severe chronic syndrome, often refractory to treatment, whose development and maintenance may involve epigenetic mechanisms. We previously demonstrated a causal relationship between miR-30c-5p upregulation in nociception-related neural structures and neuropathic pain in rats subjected to sciatic nerve injury. Furthermore, a short course of an miR-30c-5p inhibitor administered into the cisterna magna exerts long-lasting antiallodynic effects via a TGF-?1-mediated mechanism. Herein, we show that miR-30c-5p inhibition leads to global DNA hyper-methylation of neurons in the lumbar dorsal root ganglia and spinal dorsal horn in rats subjected to sciatic nerve injury. Specifically, the inhibition of miR-30-5p significantly increased the expression of the novo DNA methyltransferases DNMT3a and DNMT3b in those structures. Furthermore, we identified the mechanism and found that miR-30c-5p targets the mRNAs of DNMT3a and DNMT3b. Quantitative methylation analysis revealed that the promoter region of the antiallodynic cytokine TGF-?1 was hypomethylated in the spinal dorsal horn of nerve-injured rats treated with the miR-30c-5p inhibitor, while the promoter of Nfyc, the host gene of miR-30c-5p, was hypermethylated. These results are consistent with long-term protection against neuropathic pain development after nerve injury. Altogether, our results highlight the key role of miR-30c-5p in the epigenetic mechanisms' underlying neuropathic pain and provide the basis for miR-30c-5p as a therapeutic target.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Autoría: Francés R., Mata-Garrido J., de la Fuente R., Carcelén M., Lafarga M., Berciano M.T., García R., Hurlé M.A., Tramullas M.,

 Fuente: International Journal of Molecular Sciences, 2022, 23(22), 13994

Editorial: MDPI

 Año de publicación: 2022

Nº de páginas: 18

Tipo de publicación: Artículo de Revista

 DOI: 10.3390/ijms232213994

ISSN: 1661-6596,1422-0067

 Proyecto español: SAF2016-77732-R

Url de la publicación: https://doi.org/10.3390/ ijms232213994